Therapeutic effect of endoscopic anterior fundoplication by MUSETM in thirteen patients with gastroesophageal reflux disease / 中华消化杂志

Objective To evaluate the efficacy and safety of endoscopic anterior fundoplication by the MUSETM endoscopic stapling device in gastroesophageal reflux disease (GERD).Methods From March to November 2017,in the Department of Gastroenterology of Chinese PLA General Hospital in Beijing,The First People's Hospital Affiliated to Shanghai Jiao Tong University and Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,thirteen GERD patients who underwent the endoscopic anterior fundoplication by the MUSETM system were enrolled.The GERD health related quality of life questionnaire (GERD-HRQL) score,satisfaction of symptomatic control,questionnaire for gastroesophageal reflux disease (GERD-Q) score,the degree of esophagitis,condition of gastroesophageal flap valve,medicine administration and side effects were compared before and after the operation.Paired t test and Wilcoxon rank sum test were performed for statistical analysis.Results The total GERD-HRQL score decreased from 23 points (14 to 36 points) before operation when proton pump inhibitor (PPI) was stopped for seven days to 3 points (0 to 21 points) at three months after operation and 1 point (0 to 18 points) at six months after operation;and the differences were statistically significant (Z=-3.111 and -3.183,both P＜0.01).Among 13 patients,the GERD-HRQL score of 11 patients decreased over 50 ％ after operation.The heartburn score decreased from 21 points (13 to 29 points) before operation when PPI was stopped for seven days to 0 point (0 to 17 points) at three months after operation and 0 point (0 to 16 points) at six months after operation;and the differences were statistically significant (Z=-3.113 and -3.182,both P＜0.01).Among 13 patients,assessment of symptom control at three months after operation of seven patients were satisfactory,four patients were mostly satisfactory and two patients were unsatisfactory;assessment of symptom control at six months after operation of nine patients were satisfactory,four patients were mostly satisfactory;and the satisfaction rate were both higher than that before operation,and the differences were statistically significant (x2=16.235 and 25.159,both P＜0.01).The total GERD-Q score reduced from 13 points (8 to 17 points) before operation to 6 points (3 to 11 points) at three months after operation and 6 points (6 to 13 points) at six months after operation (Z=-3.192 and-3.066,both P＜0.01).DeMeester score decreased from 38.40 points (20.20 to 255.30 points) to 11.10 points (1.10 to 46.20 points) at six months after operation;and the percent of total time of esophageal pH＜4 reduced from 10％ (5％ to 75％) to 3％ (0 to 13％) at six months after operation;the difference was statistically significant (Z=-3.181 and-3.180,both P=0.001).There was no significant difference in esophageal motility changes before and after treatment (all P ＞ 0.05).The number of patients without esophagitis increased from three before treatment to eight after treatment.Additionally,the number of patients whose gastroesophageal flap valve was less than grade Ⅱ increased from three before operation to 11 at six months after operation.The patients were followed up for six months,among 13 patients,10 patients were completely deprived of PPI,one patient was reduced over 50％,and two patients were treated with less than 50％ reduction.All 13 patients had mild tolerable abdominal pain and sore throat within 48 hours after operation.No other adverse reactions were observed.Conclusion The endoscopic anterior fundoplication by the MUSETM is a safe and effective treatment for GERD.

Esophageal motility characteristics in gastroesophageal reflux disease patients with or without dysphagia / 中华消化杂志

Objective To investigate esophageal motility characteristics in gastroesophageal reflux disease (GERD) patients with or without dysphagia by high-resolution manometry and 24 h esophageal pH monitoring.Methods From August 2012 to November 2015,GERD patients with symptoms of acid reflux and heart burn who received 24 h esophageal pH monitoring were collected.The differences in esophageal motility were further analyzed between the GERD patients with dysphagia and without dysphagia.Student's t test,x2 test and Fisher's exact test were performed for comparison analysis.Results A total of 194 patients received 24 h esophageal pH monitoring and diagnosed as GERD,and at the same period completed esophageal high-resolution manometry.Among them,there were 17 GERD patients (8.8％) with dysphagia and 177 patients (91.2％) without dysphagia.The main classification of esophageal motility disorder of GERD patients with dysphagia was severe esophageal motility disorders (5/ 17),but the motility type of GERD patients without dysphagia patients mainly was mild esophageal motility disorders (10.2％,18/177).The integrated relaxation pressure,residual pressure of lower esophageal sphincter (LES),and contraction range at 3 cm and 11 cm above LES of GERD patients with dysphagia were all higher than those of patients without dysphagia ((9.70±0.98) mmHg (1 mmHg=0.133 kPa) vs (7.02±0.30) mmHg,(12.75±1.35) mmHg vs (9.18±0.42) mmHg,(106.80± 11.97) mmHg vs (70.82±3.48) mmHg,(82.66±10.70) mmHg vs (56.93±3.11) mmHg),and the differences were statistically significant (t=2.601,2.488,2.887,2.308,all P＜0.05).Distal esophageal contraction integral score of GERD patients with dysphagia was significantly higher than that of GERD patients without dysphagia ((2 128.94±310.47) mmHg · cm · s vs (1 029.88±90.16) mmHg · cm · s),and the difference was statistically significant (t =3.400,P =0.001).However,residual pressure of upper esophageal sphincter was significantly lower than that of patients without dysphagia ((2.84±1.21) mmHg vs (6.18±0.38) mmHg,t=-2.650,P=0.009).Conclusions Esophageal motility disorder of GERD patients with dysphagia is severer than that of patients without dysphagia.High resolution esophageal manometry can provide objective evidence of esophageal dynamics of GERD patients,which can guide the diagnosis and treatment of GERD.

Alterations in pulmonary arterial reactivity during pulmonary arterial hypertension at the early-stage of pulmonary fibrosis in rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the alterations in pulmonary arterial reactivity during pulmonary arterial hypertension at the early-stage of pulmonary fibrosis in rats.</p><p><b>METHODS</b>Sixty-six male Sprague-Dawley rats were randomly divided into 2 groups: bleomycin (BLM) group and sham group. The rats in BLM group were received single intratracheal instillation of BLM (5 mg/kg), and the rats in sham group received equal volume of 0.9% normal saline (NS). The alterations in pulmonary arterial reactivity were measured by vascular tension detected technique, the pathomorphological changes in the wall of pulmonary arteries were displayed with Hematoxylin-Eosin (HE) staining, the degree of fibrosis in lung was revealed with Masson staining, and the mean pulmonary arterial pressure was detected via a catheter in the pulmonary artery.</p><p><b>RESULTS</b>(1) The contractile response to a- adrenoceptor agonist phenylephrine (PE), of pulmonary arteries both with remaining endothelium and with removing endothelium, from BLM-treated rats , was reduced significantly, compared with sham rats (P both < 0.05). (2) The relaxant response to the endothelially dependent vasodilator acetylcholine (Ach), of pulmonary arteries with remaining endothelium, from BLM-treated rats, was also reduced, compared with sham rats (P < 0.01). (3) In sham rats, the contractile response to (omega) -nitro-L-arginine methyl ester (L-NAME) plus PE, of pulmonary arteries with remaining endothelium, was enhanced, compared with that to PE alone (P < 0.01), while in BLM group, the contractile responses to L-NAME plus PE, of pulmonary arteries with remaining endothelium, was not different from that to PE alone (P > 0.05). (4) In BLM group, vascular endothelial cells lost. (5) In BLM group, the initial stage of fibrogenesis was observed in lungs, and the mean pulmonary arterial pressure increased, compared with that in sham group (P < 0.05).</p><p><b>CONCLUSION</b>The abnormal responsibility of pulmonary arteries occurred during pulmonary arterial hypertension at the early-stage of pulmonary fibrosis in rats.</p>

The effect of baicalein on bleomycin-induced fibrosis in lungs of rats / 中国应用生理学杂志

<p><b>AIM</b>To explore the effect of baicalein (Bai-Chinese Traditional Medicine) on bleomycin (BLM)-induced fibrosis in lungs of rats and its possible mechanism.</p><p><b>METHODS</b>Sixty-eight male Sprague-Dawley rats were randomly divided into 4 groups: BLM plus Bai group, BLM plus normal saline (NS) group, NS plus Bai group, and NS plus NS group. The rats were received single intratracheal instillation of BLM (5 mg kg(-1) bw) or equal volume of NS as control, and received intraperitoneal injection o f Bai (12.5 mg x kg(-1) bw) or the same volume of NS asvehicle for 28 d. The hydroxyproline content, the collagen area, the mRNA expression of Col I (alpha), and the myofibroblasts in lung were examined.</p><p><b>RESULTS</b>The content of hydroxyproline, the percentage of collagen area, the mRNA expression of Col I (alpha), and the amount of myofibroblast were increased in lungs of rats on day 28 after intratracheal instillation of BLM, compared with that in lungs of the control rats, respectively( All P < 0.01). The above abnormal changes were ameliorated by Bai (12.5 mg x kg(-1) x d(-1) ip, x 28 d (All P < 0.05).</p><p><b>CONCLUSION</b>Bai has anti-action on BLM-induced fibrosis in lung, and that the above action of Bai is related to the blockage of synthesis of type I collagen and the decrease of myofibroblast in lung.</p>

The effects of aminoguanidine inhalation on bleomycin-induced fibrosis in lungs / 中国应用生理学杂志

<p><b>AIM</b>To explore the effects of aminoguanidine (AG) inhalation on bleomycin (BLM)-induced fibrosis in lungs of rats and its possible mechanism.</p><p><b>METHODS</b>Sixty male Sprague-Dawley rats were randomly divided into 4 groups: BLM plus normal saline (NS) group, BLM plus 10 mmol/L AG group, BLM plus 50 mmol/L AG group, and NS plus NS group. At the same day when administrated by single intratracheal instillation of BLM (5 mg/kg) or equal volume of NS as control, the rats received NS (the same volume as AG) or AG inhalation (10 mmol/L AG, or 50 mmol/L AG, 5 min/each time, 2/day) for 30 d. The nitrite/nitrate (NO2-/NO3-) content of plasma in pulmonary artery, hydroxyproline content and the pathological changes in lungs, as well as lipid peroxide (LPO) content of plasma in pulmonary artery were examined.</p><p><b>RESULTS</b>The NO2-/NO3- content of plasma in pulmonary artery was increased in rats on day 14 after intratracheal instillation of BLM, compared with that of the control rats (P < 0.01). The hydroxyproline content in lung, the grade of pulmonary alveolitis and the content of LPO of plasma in pulmonary artery were increased in rats on day 30 after intratracheal instillation of BLM, compared with that of the control rats, respectively (P < 0.05, P < 0.01, P < 0.01). The above-mentioned changes were ameliorated by AG inhalation (10 mmol/L AG, or 50 mmol/ LAG, 5 min/each time, 2/day) for 30 d (P < 0.01, P < 0.05, P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>AG inhalation has anti-action on BLM-induced fibrosis in lung, which might be related to blockage of oxidative injury in lung.</p>

Expression of connective tissue growth factor in pulmonary artery at the early-stage of pulmonary fibrosis / 生理学报

To ascertain whether connective tissue growth factor (CTGF) participates in the remodeling of pulmonary artery at the early-stage of bleomycin (BLM)-induced pulmonary fibrosis, mean pulmonary arterial pressure, the expression of type I and type III collagens, and the expression and location of CTGF in pulmonary artery and arteriole were investigated in the present study. Sprague-Dawley rats received instillation of BLM [5 mg/kg body weight, in 0.5 mL of normal saline (NS)] or instillation of the same amount of NS as control. Mean pulmonary arterial pressure was detected via a catheter in the pulmonary artery. Type I and type III collagens were examined with Sirius red staining under polarized light. CTGF expression was investigated by using immunohistochemistry, and was represented as average optical density and percentage of positive area of CTGF. The mean pulmonary arterial pressure was higher in rats on day 14 after BLM instillation [(19.5+/-2.9) mmHg] than that in the control rats [(14.8+/-1.2) mmHg] (P<0.05). The type I and type III collagens were increased both in pulmonary artery and arteriole of rats on day 14 after BLM instillation, compared with those in the control rats (P<0.05, P<0.01, respectively). The ratio of type I/III collagens in pulmonary artery was also higher in BLM-treated rats than that in the control rats (P<0.05). The values of average optical density of positive CTGF staining were increased both in pulmonary artery (0.37+/-0.02) and arteriole (0.40+/-0.03) of rats on day 14 after BLM instillation, compared with those in the control rats (artery, 0.34+/-0.01; arteriole, 0.29+/-0.01) (both P<0.05). The percentages of positive area of CTGF were higher in pulmonary artery (8.40+/-1.13) and arteriole (12.4+/-2.0) of rats on day 14 after BLM instillation than those in the control rats (artery: 1.42+/-0.63; arteriole: 1.16+/-0.34), respectively (both P<0.05). The increased positive CTGF staining areas were mainly located in the endothelium and smooth muscle layer. It is therefore concluded that CTGF expression increases in the endothelium and smooth muscle layer of pulmonary artery and arterioles during high pulmonary arterial pressure and remodeling of pulmonary artery at the early-stage of BLM-induced pulmonary fibrosis, and that the increased CTGF might be one of the mechanisms of maintenance and development of pulmonary hypertension.

The effect of time parameters of cerebral ischemic preconditioning on its protective effect against global cerebral ischemic injury in rats / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effects of the duration of cerebral ischemic preconditioning(CIP) and interval between CIP and the subsequent ischemic insult on the protection of CIP against delayed neuronal death (DND) in the CA1 hippocampus normally induced by brain ischemic insult.</p><p><b>METHODS</b>Four-vessel occlusion cerebral ischemic model of rats (54) was used. The brain of the rats was sectioned and stained with thionin to show DND in the CA1 hippocampus.</p><p><b>RESULTS</b>No DND was found in the hippocampus of the rats subjected to sham operation and CIP, in which 3 min cerebral ischemic preconditioning was performed. Obvious destruction of the CA1 hippocampus was found in brain ischemic insult group, in which histological (HG) was 2-3 in 6 min and 10 min ischemia subgroups and grade 3 in 15 min ischemia subgroup. In CIP + brain ischemic insult group, no obvious neuronal damage was found in 3 min-3d-6 min (CIP for 3 min was followed by a brain ischemic insult for 6 min at an interval of 3 d, the same as the following) and 3 min-3 d-10 min groups, indicating that CIP effectively protected neurons of the CA1 hippocampus against DND normally induced by ischemic insult for 6 or 10 min. However, in 3 min-1 d-10 min and 3 min-3 d-15 min groups, the protective effect of CIP was lower than that in the 3 min-3 d-10 min group. The quantitative analysis of the protective effect of CIP on the CA1 hippocampal neurons showed that there was no significant difference in protecting number and protecting index between 3 min-3 d-6 min and 3 min-3 d-10 min groups (P > 0.05). However, the growth index in 3 min-3 d-10 min group was obvious larger than that in 3 min-3 d-6 min (P < 0.05).</p><p><b>CONCLUSION</b>Although the protective effects of CIP in 3 min-3 d-6 min and 3 min-3 d-10 min groups were similar, the protective effect of CIP in 3 min-3 d-10 min group was sensitively found. Maximal protective potential of CIP could be induced when using the time parameters of 3 min-3 d-10 min to establish the model of global cerebral ischemic tolerance.</p>

Effects of the metabotropic glutamate receptor ligands on the induction of brain ischemic tolerance in rats / 中国组织工程研究

BACKGROUND: Metabotropic glutamate receptor(mGluR) is G-protein coupled membrane receptors, which participate in various physiology or pathology process in brain, but how it induce brain ischemic tolerance(BIT)is unclear.OBJECTIVE: To study roles of mGluR2/3 and mGluR1/5 in the BIT induction.DESIGN: Randomized controlled study based on experimental animals.SETTING: Neurological department of provincial hospital and pathophysiological department of basic institute in a university.MATERIALS: The study was conducted at the Pathophysiological Department, Institute of Basic Medicine, Hebei Medical University from May 2002 to May 2003. Totally 64 healthy male SD rats were selected from the Experimental Animal Center of Hebei Medical University. Glial fibrillary acidic protein (GFAP) antibody, MTPG and(s)-4C3HPG were got from Sigma Company.INTERVENTIONS: 4 vessel occlusion(4VO) brain ischemic models in rats stained with thionine staining and GFAP immunohistochemistry staining. were used. Sixty-four rats, of which bilateral vertebral arteries were occluded permanently by electrocautery, were divided into the following 8groups: sham operation group, cerebral ischemic preconditioning(CIP)group, ischemic insult group; BIT group; MTPG + sham operation group;MTPG+BIT group; MTPG+ischemia group and(s) -4C3HPG+BIT coup. All the rats were killed 7 days after the operation or the final ischemic treatment. Cerebral sections were selected and stained with thionine staining and GFAP immunohistochemistry staining.MAIN OUTCOME MEASURE: The changes of the morphologic hippocampal pyramidal cell and GFAP expression of astrocyte.RESULTS: ① The 8 minutes ischemic insult increased the histological grade(HG) in CA1 area, decreased the pyramidal neuronal density(ND)and increased the expression of GFAP significantly( P ＜ 0.05) . ② The above changes were not observed in the BIT group, indicating that the CIP could protect pyramidal neurons against the 8-minute ischemic insult. ③The protective effects of the CIP were blocked by MTPG or(s)-4C3HPG, as manifested by significant increases in HG and decreases in ND in the groups of MTPG + BIT, MTPG + ischemia and(s)-4C3HPG + BIT( P ＜ 0.05).CONCLUSION: MTPG or (s) -4C3HPG could block the induction of BIT induced by CIP, but mGluR2/3 or mGluR1/5 could participate in the induction of BIT by which protect effect of mGluR is further induced.

Modulatory action of endogenous and exogenous nitric oxide on survival of alveolar macrophages from normal and bleomycin-treated rats / 生理学报

To investigate the modulatory action of endogenous and exogenous nitric oxide (NO) on survival of alveolar macrophages (AMs) in different cellular states, AMs from normal rats (normal AMs) and from bleomycin (BLM)-treated rats (BLM AMs) were incubated by sodium nitroprusside (SNP, NO donor) and L-arginin (L-Arg, NO precursor), respectively. The survival of AMs was evaluated by apoptosis and cell cycles. The molecular mechanisms were investigated by the contents of Bcl-2, Bax proteins in AMs. The results are as follows: (1) The degree of BLM AMs apoptosis was higher than that of normal AMs; the number of BLM AMs in G(0)/G(1) phases was less than that of normal AMs; there was no significant difference in S+G(2)M phases between the number of BLM AMs and that of normal AMs. (2) Down-regulation of Bcl-2 and up-regulation of Bax occurred in BLM AMs, compared to those in normal AMs. (3) Apoptosis of AMs, either normal AMs or BLM AMs, was induced by both SNP and L-Arg, when compared to their respective control; only the number of BLM AMs in S+G(2)M phases was increased by L-Arg. (4) SNP and L-Arg induced a down-regulation of Bcl-2 and an up-regulation of Bax proteins in normal AMs, but did not induce the same change pattern in BLM AMs. (5) The Bax in BLM AMs was down-regulated by L-Arg. It is concluded that NO can induce the apoptosis of BLM AMs and normal AMs; that Bcl-2 and Bax are implicated in NO-induced apoptosis of normal AMs, whereas they are not involved in that of BLM AMs, suggesting the differential molecular mechanisms underlying the NO-induced apoptosis of normal AMs and BLM AMs; and that endogenous NO promotes proliferation of BLM AMs, which might be associated with down-regulation of Bax.

Limb ischemic preconditioning attenuates apoptosis of pyramidal neurons in the CA1 hippocampus induced by cerebral ischemia-reperfusion in rats / 生理学报

The purpose of this study was to investigate the effects of limb ischemic preconditioning (LIP) on apoptosis of pyramidal neurons in the CA1 hippocampus induced by global cerebral ischemia-reperfusion in rats. Forty-six rats whose bilateral vertebral arteries were occluded permanently were assigned to one of four groups: sham group, limb ischemia group, cerebral ischemia group and LIP group. LIP was performed by occluding the bilateral femoral arteries for 10 min 3 times in an interval of 10 min. Global cerebral ischemia was underwent by occluding the bilateral common carotid arteries for 8 min immediately after LIP. Assays for apoptosis of the hippocampal neurons were biologically and morphologically performed using gel electrophoresis, TUNEL and AO/EB staining. Characteristic DNA ladder was clearly visualized with gel electrophoresis in the hippocampus in cerebral ischemia group, but not in LIP group. The number of TUNEL-positive cells in the CA1 hippocampus was significantly reduced by LIP from 69.8+/-12 (cerebral ischemia group) to 17.8+/-5.8 (P<0.01). AO/EB staining also showed a reduction of apoptosis in LIP group compared with cerebral ischemia group. These results suggest that LIP can inhibit hippocampal neuronal apoptosis induced by cerebral ischemia-reperfusion, which contributes to the protection against the delayed neuronal death induced by cerebral ischemic insult.

Changes of COX-2 expression in the dorsal horn of the spinal cord during formalin-induced inflammatory pain and hyperalgesia in rats / 中国应用生理学杂志

<p><b>AIM</b>To observe the changes of cyclooxygenase-2 (COX-2) expression and especially the time course of the changes in dorsal horn of the spinal cord during formalin-induced inflammatory pain and hyperalgesia in rats.</p><p><b>METHODS</b>COX-2 immunohistochemistry staining was used in rat formalin pain model.</p><p><b>RESULTS</b>Compared with control group the number and immunostaining density of COX-2 immunoreactive cells in the laminae I-VI of the dorsal horn of the spinal cord increased significantly 4 h, 1 d and 3 d after formalin injection (P < 0.05). The most obvious increase was observed 1 d after the injection.</p><p><b>CONCLUSION</b>COX-2 in the dorsal horn of the spinal cord is involved in the formalin-induced inflammatory pain and hyperalgesia.</p>

Limb ischemic preconditioning decreases hippocampal ischemia/reperfusion injuries in rats / 中国应用生理学杂志

<p><b>AIM</b>To explore the effects of limb ischemic preconditioning (LIP) on cerebral ischemia/reperfusion injuries.</p><p><b>METHODS</b>Thirty six wistar rats, of which bilateral vertebral arteries were occluded permanently, were randomly divided into the following 6 groups: control group, cerebral ischemic group, limb ischemic group, LIP 0 d group (cerebral ischemia was given immediately after LIP), LIP 1 d group (cerebral ischemia was given 1 d after LIP) and LIP 2 d group (cerebral ischemia was given 2 d after LIP). Global cerebral ischemia was performed by four vessels occlusion in rats. LIP was performed by occluding the bilateral femoral arteries for 10 min 3 times in a interval of 10 min. The histological grade and pyramidal neuronal density in the CA1 hippocampus were measured to quantitate the degree of hippocampal injury under thionin staining.</p><p><b>RESULTS</b>The histological grade was increased and the pyramidal neuronal density was decreased in the CA1 hippocampus of the cerebral ischemic group (P < 0.01). The damage of the CA1 hippocampus in LIP 0 d group was significantly diminished, which represented by decreased histological grade and increased neuronal density compared with the cerebral ischemic group (P < 0.01). But the CA1 hippocampus still showed obvious injuries in the LIP 1 d and LIP 2 d group.</p><p><b>CONCLUSION</b>LIP performed immediately prior to cerebral ischemia could confer obvious protective effects on CA1 hippocampus against cerebral ischemia/reperfusion injuries. But LIP performed 1 d and 2 d prior to cerebral ischemia could not afford the protection against injuries induced by cerebral ischemia/reperfusion.</p>

Effects of cysteamine on the plasma levels of SS and some metabolic hormones in adult geese / 中国应用生理学杂志

<p><b>AIM</b>To know the effect of cysteamine (CS) on the plasma levels of somatostatin (SS) and some metabolic hormones in adult geese.</p><p><b>METHODS</b>Fourteen adult crossbred geese (Chuan white x Tai lake) fitted with chronic wing vein cannulas were used in this study to evaluate the effect of CS on SS, TSH, T3 and T4 levels. The experiment was consisted of control and treated phase. The diet was added CS at dosage of 100 mg/kg bw on the first day of the treated phase. The blood samples were collected from the cannulas and analyzed by radioimmunoassay.</p><p><b>RESULTS</b>The plasma SS concentration was (1.87 +/- 0.10) microg/L in control phase. Whereas SS concentrations on day 1, 3, 5, 7 of treated phase were decreased markedly (P < 0.05 or P < 0.01). Thereafter it was rose on the seventh day, however it was still lower than that of control. The thyroid stimulating hormone (TSH) content (2.45 +/- 0.31 mIU/L) was significantly decreased by 21.63% (P < 0.01) on day 1, and 18.37% (P > 0.05) on day 3 and day 5. Comparing with control phase (5.41 +/- 0.98 microg/L), T4 contents were elevated by 60.26% (P < 0.01), 43.25% (P < 0.01), 37.15% (P < 0.01) and 16. 82% (P < 0.01) respectively on day 1, 3, 5, 7. T3 level was (1.05 +/- 0.06) microg/L in control phase, whereas the levels was significantly increased by 36.19% (P < 0.01) on day 3. Also, the insulin concentration was higher than that of control (4.43 +/- 0.41 mU/ L) by 18.28% (P < 0.05) on the day 5.</p><p><b>CONCLUSION</b>These results indicate that CS can decrease the plasma SS and TSH levels, whereas increase the levels of T4, T3 and insulin, therefore change metabolism, improve the nutrition transform and accelerate the growth in geese.</p>

MK-801 inhibits formalin-induced cyclooxygenase-2 expression in the dorsal horn of the spinal cord in rats / 生理学报

To investigate the effect of N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 on the formalin-induced cyclooxygenase-2 (COX-2) expression in the dorsal horn of the rat spinal cord. Forty-eight male Sprague-Dawley rats were divided into 4 groups: control, formalin, formalin+normal saline (NS) and formalin+MK-801 groups. Rats in formalin, formalin+NS and formalin+MK-801 groups were subcutaneously injected with 0.2 ml 5% formalin into the plantar surface of the right hind paw. NS or MK-801 solution (10 microl) was intrathecally injected under transient ether anesthesia 15 min prior to the formalin injection in the formalin+NS and formalin+MK-801 groups, respectively. Flinch reflex was measured within 1 h after the formalin injection and expression of COX-2 in the dorsal horn of the L(5) segment of the spinal cord was assayed 24 h after the formalin injection using immunohistochemistry. Formalin evoked a biphasic flinch reflex. MK-801 produced a limited effect on the flinch reflex of phase 1, but produced significant and dose-dependent suppression on the flinch reflex of phase 2. The number and immunostaining density, shown by grey degree which was inversely proportional to the immunostaining density, of immunoreactive soma in the superficial (mainly I-II) and deep (IV-VI) laminae of the L(5) spinal cord in formalin and formalin+NS groups increased significantly, in contrast to those in the control group (p<0.01). The number and immunostaining density of immunoreactive soma decreased significantly in formalin+MK-801 group, in comparison with the formalin+NS group (p<0.05). The degree of the decrease was proportional to the dosage of MK-801 used. In addition, there were some immunoreactive processes especially in the superficial laminae, which extended as a continuous band across the dorsal horn after the formalin injection. Change in immunostaining density of the processes after administration of MK-801 was similar to that in the immunoreactive soma. The results showed that intrathecal injection of MK-801 significantly inhibited the increase of COX-2 expression in the spinal dorsal horn induced by the formalin injection in a dose-dependent manner, suggesting that the activation of NMDA receptor is one of the mechanisms for the formalin-induced increase of COX-2 expression in the spinal dorsal horn.

Effects of alpha-methyl-(4-tetrazolyl-phenyl) glycine on the induction of hippocampal ischemic tolerance in the rat / 生理学报

To explore the role of metabotropic glutamate receptor 2/3 mGluR 2/3 in the induction of brain ischemic tolerance (BIT), the influences of mGluR2/3 antagonist alpha-methyl-(4-tetrazolyl-phenyl) glycine (MTPG) on the induction of BIT and expression of glial fibrillary acidic protein (GFAP) in the hippocampus were observed using thionin staining and GFAP immunohistochemical staining in a rat brain ischemic model with four-vessel occlusion (4VO). Fifty-four rats, of which bilateral vertebral arteries were occluded permanently by electrocautery, were divided into 5 groups: (1) sham operated group (n=8): the bilateral carotid common arteries (BCCA) were separated, but the blood flow was not blocked; (2) ischemia group (n=8): the blood flow of BCCA was blocked for 8 min; (3) ischemic preconditioning (IP) group (n=8): the blood flow of BCCA was occluded for 3 min as a cerebral ischemic preconditioning (CIP), and then the rats were exposed to an 8-min brain ischemic insult 24 h after the CIP; (4) MTPG+IP group (n=22): MTPG was administered 20 min before the CIP, then the rats were exposed to an 8-min brain ischemia insult 24 h after the CIP. In order to examine dosage dependency in the effect of MTPG, 4 dosages of MTPG (0.4, 0.2, 0.04 and 0.008 mg) were administered; (5) MTPG+ischemia group (n=8): an ischemic insult for 8 min was given 24 h after the administration of MTPG (0.2 mg). MTPG was injected into the right lateral cerebral ventricle. The results obtained are as follows. (1) Ischemic insult for 8 min increased the histological grade (HG) and reduced the neuronal density (ND) significantly, and also increased the expression of GFAP significantly (P<0.05 vs sham-operated group). (2) In the IP group, the above changes were not observed, indicating that CIP could protect pyramidal neurons against the ischemic insult. (3) The protective effects of CIP were blocked by MTPG, as manifested by the significant increase in HG and decrease in ND in the MTPG+IP group (P<0.05 vs sham-operated group). The changes were dose-dependent. (4) No obvious difference in the HG, ND and expression of GFAP was detected between the groups of MTPG+ischemia and ischemia. The above results indicate that MTPG blocks the induction of BIT induced by CIP, suggesting that mGluR2/3 participates in the induction of BIT.

Effect of nitric oxide synthase inhibitor L-NAME on the induction of brain ischemic tolerance in rats / 生理学报

To explore the role of NO in the induction of brain ischemic tolerance (BIT) in vivo, the effect of nitric oxide synthase (NOS) inhibitor L-NAME on the induction of BIT induced by cerebral ischemic preconditioning (CIP) was investigated in the hippocampal CA1 subfield in CIP and ischemic insult models established by rat four-vessel occlusion using brain tissue section and thionine staining methods. Fifty-four male Wistar rats were divided into 6 groups: (1) sham-operated group (n=6): bilateral common arteries were separated without occluding the cerebral blood flow; (2) ischemia group (n=6): an ischemic insult for 10 min was given; (3) CIP+ischemia group (n=6): 3-min CIP was preformed 72 h prior to 10-min ischemic insult; (4) L-NAME group (total n=24, n=6 for each subgroup): L-NAME (5 mg/kg, i.p.) was administered 1 h prior to CIP and 1, 12 and 36 h after CIP, respectively. Other procedures were the same as those for the CIP+ischemia group; (5) L-NAME+L-Arg group (n=6): L-NAME (5 mg/kg, i.p.) and L-Arg (300 mg/kg, i.p.) were administered 1 h prior to CIP, other procedures were the same as those for the L-NAME group; (6) L-NAME+ischemia group (n=6): L-NAME (5 mg/kg, i.p.) was administered 72 h before the 10-min ischemic insult. The results showed that (1)10-min ischemic insult resulted in an increase in the histological grade (indicating a more serious tissue injury) and a decrease in pyramidal neuronal density (P<0.01); (2) the histological grade and neuronal density in hippocampal CA1 in the CIP+ischemia group were similar to those in the sham-operated group (P>0.05); (3) in the L-NAME group, administration of L-NAME brought about an increase in the histological grade and a decrease in neuronal density (P<0.01), suggesting that L-NAME blocked the protection of CIP; (4) the neuronal damage in L-NAME+L-Arg group was slighter than that in the L-NAME group, but still more serious than that in the CIP+ischemia group, suggesting that L-Arg partly reversed the blocking effect of L-NAME; (5) the morphological representations in L-NAME+ischemia group were basically similar to those in the ischemia group. The results mentioned above indicate that NO is involved in the induction of BIT in vivo. The blocking effect of L-NAME administered at 36 h after CIP was obviously weaker than the effects of L-NAME administered 1 h prior to CIP, and 1 or 12 h after CIP. It is suggested that NO is involved in the induction of BIT at an early stage and that the involvement might take place via activating cascades of the events.

Effects of the metabotropic glutamate receptor ligand(s)-4C3HPG on the induction of brain ischemic tolerance in the rat / 中国应用生理学杂志

<p><b>AIM</b>To explore roles of metabotropic glutamate receptor1/5 (mGluR1/5) in the induction of brain ischemic tolerance (BIT) induced by cerebral ischemic preconditioning (CIP), influences of mGluR1/5 ligand (s)-4-carboxy-3-hydroxy- phenylglycine ((s)-4C3HPG) on the induction of BIT and expression of glial fibrillary acidic protein (GFAP) in the hippocampus were observed.</p><p><b>METHODS</b>Thionin staining and GFAP immunohistochemistry staining in rat 4 vessel occlusion (4VO) brain ischemic model was used. Thirty-six rats, of which bilateral vertebral arteries were occluded permanently by electrocautery, were divided into the following 4 groups: sham group; ischemic insult group, BIT group and (s)-4C3HPG group. According to dosages of (s)-4C3HPG used, the (s)-4C3HPG group, was further divided into 0.2 mg, 0.04 mg and 0.008 mg subgroups. All the rats were killed 7 d after the operation or the final ischemic treatment.</p><p><b>RESULTS</b>(1) The ischemic insult for 8 min increased the histological grade (HG), decreased the pyramidal neuronal density (ND) and increased the expression of GFAP significantly (P < 0.05 vs sham) (2) The CIP prevented the above injury changes in the BIT group. (3) The protective effects of the CIP were blocked by (s)-4C3HFG, as manifested by significant increases in HG and decreases in ND in the (s)-4C3HPG group (P < 0.05 vs sham and BIT groups). The changes were proportional with the dosages of (s)-4C3HPG used.</p><p><b>CONCLUSION</b>(s)-4C3HPG could block the induction of BIT induced by CIP, suggested that mGluR1/5 participate in the induction of BIT.</p>

Intrathecal injection of Sar9, Met(O2)11-substance P, neurokinin-1 receptor agonist, increases nitric oxide synthase expression and nitric oxide production in the rat spinal cord / 生理学报

In the spinal cord, nitric oxide (NO) pathway is involved in pain and hyperalgesia, and nitric oxide synthase (NOS) expression and NO production are upregulated following several noxious and lesion stimuli. However, the mechanism of the increases is yet not well understood. The present study was designed to address the question of whether substance P (SP) released in the spinal cord enhances NOS expression and NO production of the spinal cord in rats. [Sar(9), Met(O2)(11)]-substance P (Sar-SP), a neurokinin-1 (NK-1) receptor agonist, was administered by intrathecal injection via L(5)-L(6) intervertebral space to induce nociception. The pain threshold was determined by hot water induced tail flick test. NOS expression of the L(5) segment of the spinal cord was determined using NADPH-d histochemical staining. NO production of the lumbar enlargement of the spinal cord was determined by assaying NO3(-) and NO2(-), the end product of NO metabolism, using the method of aqua fortis reduction. We found that (1) intrathecal injection of Sar-SP (6.5 nmol) elicited a characteristic, caudally directed, nociceptive behavioural response consisting of intense biting, licking and scratching episodes. Tail flick test showed decrease in pain threshold. (2) following the behavioural responses, the NOS expression level, including the number and the staining density of the NADPH-d reactive cells, increased in the superficial portion of the dorsal horn (Laminae I-II) and the grey matter surrounding the central canal (LaminaX) of the L(5) segment of the spinal cord after the Sar-SP intrathecal injection. At the same time, NO production in the enlargement of the spinal cord increased. (3) The decreased pain threshold and the increases in NOS expression and NO production could be substantially inhibited by intrathecal injection of [[D-Arg(1), D-Trp(7,9), Leu(11)]-substance P] (spantide) (5 microg), a non-selective antagonist of NK-1 receptor, 5 min prior to the Sar-SP injection. It might be concluded that the release of SP resulted from nociceptive afferents increased NOS expression and NO production of the rat spinal cord.

Effects of clenbuterol on nitrogen metabolism and G6PDH activity of rat hepatocyte / 药学学报

<p><b>AIM</b>To study the effects of beta 2-adrenergic receptor-selective agonist clenbuterol on nitrogen metabolism and glucose-6-phosphate dehydrogenase activity of rat hepatocyte and its pharmacological mechanism.</p><p><b>METHODS</b>Biochemical methods were used to study the influence of clenbuterol on urea-nitrogen concentration of hepatocyte culture medium, 3H-leucine incorporation into hepatocyte, insulin-like growth factor I (IGF-I) production and glucose-6-phosphate dehydrogenase (G6PDH) activity of rat hepatocyte.</p><p><b>RESULTS</b>The results showed that urea-nitrogen production by cultured rat hepatocytes was markedly affected with clenbuterol treatment (1 x 10(-6) mol.L-1), urea-nitrogen concentration of culture medium was decreased by 25.51% (P < 0.05) compared with control. The inhibitory effect of hepatocyte urea-nitrogen production of clenbuterol was blocked by propranolol, a beta-adrenoreceptor antagonist (1 x 10(-6) mol.L-1), but hepatocyte urea-nitrogen level was not affected with propranolol treatment only (P > 0.05). The content of 3H-leucine incorporation in rat hepatocyte was significantly increased by 23.35% (P < 0.05) with clenbuterol-treatment (1 x 10(-6) mol.L-1), and the enhanced effect of 3H-leucine incorporation into hepatocyte was antagonized by propranolol (1 x 10(-6) mol.L-1. The level of 3H-leucine incorporation of rat hepatocyte was not influenced by propranolol alone. IGF-I production of rat hepatocyte might be affected by clenbuterol. IGF-I concentration of culture medium was increased by 39.46% with clenbuterol (1 x 10(-6) mol.L-1), but no significant difference was found compared with the control (P > 0.05). Moreover, G6PDH activity of rat hepatocyte was significantly decreased by 43.36% (P < 0.05) with clenbuterol treatment (1 x 10(-6) mol.L-1), and the declined effect of clenbuterol was antagonized by propranolol. G6PDH activity of rat hepatocyte was not affected on condition that propranolol was administered alone (P > 0.05).</p><p><b>CONCLUSION</b>It is suggested that clenbuterol may regulate nitrogen and fat metabolism by means of increasing nitrogen retention and protein synthesis, and decreasing G6PDH activity of rat hepatocyte for pharmacological effects.</p>

Effects of clenbuterol on the hepatic flux of nitrogen, VFA and glucose in sheep / 中国应用生理学杂志

<p><b>AIM</b>To examine the liver mechanism with which clenbuterol (CL) is explained how to affect growth metabolism.</p><p><b>METHODS</b>The technique of chronic poly catheter was used to study the effects of CL (0.8 mg/kg b w) on the hepatic flux of nitrogen, VFA and glucose in 4 sheep.</p><p><b>RESULTS</b>The urea-nitrogen flux in CL-treated period always was lower than that in control during 24 h. The average flux of urea-nitrogen in hepatic and portal vein were decreased by 16.86% (P < 0.01) and 15.51% (P < 0.05), respectively, compared with that of control. The peptide level in hepatic vein was decreased with the treatment of CL, average flux of peptide was decreased by 38.71% (P < 0.01). But the peptide level of portal vein in CL treatment period was similar to control. Moreover, VFA level in the portal vein was enhanced by CL, the average flux of acetate in portal vein was increased by 19.49% (P < 0.01). No difference of VFA level in hepatic vein was noted between CL-treated period and control. In addition, the glucose flux in hepatic vein was obviously increased with CL treatment, the average flux of glucose was increased by 25.96% (P < 0.01). And glucose flux in portal vein was also elevated during CL-treated period.</p><p><b>CONCLUSION</b>CL can affect growth metabolism of animal with increasing nitrogen deposition, improving absorption and utilization of VFA and enhancing glucose synthesis in sheep liver.</p>