Effect of Chinese herbal compound Naofucong () on the inflammatory process induced by high glucose in BV-2 cells / 中国结合医学杂志

<p><b>OBJECTIVE</b>To determine the effect of medicated serum of Chinese herbal compound Naofucong (, NFC) on the microglia BV-2 cells viability and the transcription and expression of interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) in microglia BV-2 cells to further explore the mechanisms underlying the protective effect of NFC on inflammatory process induced by high glucose.</p><p><b>METHODS</b>The microglia BV-2 cells incubated in vitro were divided into different groups: the control group (25 mmol/L glucose), the model group (75 mmol/L glucose), high glucose media containing different dose medicated serum of NFC. After being cultured for 24 h, changes in IL-6 and TNF-α were measured by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. The expression of surface marker CD11b of activated microglia was measured by confocal laser scanning microscope and Western blot. Nuclear factor-κB (NF-κB) p-p65 expression was analyzed by Western blot.</p><p><b>RESULTS</b>The model group obviously increased the expression of microglial surface marker CD11b and NF-κB p-p65 (all P<0.01), induced a signifificant up-regulation of release and the mRNA expression of IL-6 and TNF-α (P<0.01 or P<0.05). The medicated serum of NFC could obviously down-regulate the transcription and expression of surface marker CD11 b and NF-κB p-p65 (all P<0.01), and inhibit the mRNA and protein expression (P<0.01 or P<0.05) of inflflammatory cytokines, such as IL-6 and TNF-α, in microglia BV-2 cells cultured with high glucose for 24 h.</p><p><b>CONCLUSIONS</b>The inhibition of microglial activation and IL-6 and TNF-α expression induced by high glucose may at least partly explain NFC therapeutic effects on diabetes-associated cognitive decline diseases. Its underlying mechanism could probably be related to the inhibition of NFC on NF-κB phosphorylation.</p>

Effects of Guhong Injection on Expression of Vascular Endothelial Growth Factor in Cortex after Cerebral Ischemia-reperfusion in Rats / 中国康复理论与实践

@#Objective To study the effects of Guhong injection on the expression of vascular endothelial growth factor (VEGF) in the cortex 14 days after cerebral ischemia-reperfusion. Methods 30 male Sprague-Dawley rats were divided into sham group (n=6), ischemia group (n=6), aceglutamide injection group (n=6), Honghua injection group (n=6) and Guhong injection group (n=6). The middle cerebral arteries of all the rats were occluded for 2 hours and reperfusion, except the sham group. Drugs were administered once a day 24 hours after reperfusion. The expression of VEGF in cortex was detected with enzyme-linked immunosorbent assay (ELISA) 14 days after reperfusion. Results The expression of VEGF decreased in the ischemia group compared with the sham group (P<0.001), and it increased both in the aceglutamide and Guhong injection groups compared with the ischemia group (P<0.05). Conclusion Guhong injection can significantly increase the expression of VEGF in the cortex 14 days after ischemia-reperfusion, which may be one of the ways for neuro-protection.

Propofol may protect PC12 cells from β-amyloid₂₅₋₃₅ induced apoptosis through the GSK-3β signaling pathway / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>There are two major pathological hallmarks of Alzheimer's disease. One is the progressive accumulation of beta-amyloid (Aβ) in the form of senile plaques; the other is hyperphosphorylated tau, causing neuronal apoptosis. Some inhalation anesthetics, such as isoflurane and desflurane, have been suggested to induce Aβ accumulation and cause AD-like neuropathogenesis. Whether intravenous anesthetics have similar effects is still unclear. We therefore set out to determine the relationship between propofol and AD-like pathogenesis.</p><p><b>METHODS</b>PC12 cells were cultured in serum-free medium for 12 hours prior to drug treatment. Various concentrations from 5 µmol/L to 80 µmol/L of aggregated Aβ25-35 were added to determine a proper concentration for further study. After exposure to 10 µmol/L Aβ25-35 alone or with 20 µmol/L propofol for 6 hours, PC12 cell viability was determined by MTT assay. Western blotting and immunocytochemical staining were performed to observe the protein expression of the Bcl-2 family, tau phosphorylation at different sites, and tau protein kinases and phosphatases.</p><p><b>RESULTS</b>Aβ25-35 induced a decrease in PC12 cell viability in a dose-dependent manner. Exposure to 10 µmol/L Aβ25-35 for 6 hours resulted in the mild cell survival, accompanied by a decline in Bcl-2, and an increase in phosphorylation of GSK-3β and tau at different sites. Compared with the Aβ25-35 group, cells treated with propofol alone showed no significant difference, while cells co-incubated with propofol and Aβ25-35 showed a significantly higher survival rate (P < 0.01 or P < 0.05). Tau phosphorylation at Ser396, Ser404 and Thr231 and the level of GSK-3β in PC12 cells increased after exposure to 10 µmol/L Aβ25-35. Co-incubation with propofol attenuated cellular apoptosis by inhibiting tau phosphorylation.</p><p><b>CONCLUSIONS</b>These data indicate that propofol may protect PC12 cells from Aβ25-35-induced apoptosis and tau hyperphosphorylation through the GSK-3β pathway, therefore it may be a safer anesthesia for AD and elderly patients.</p>

Analgesic effect of gabapentin in a rat model for chronic constrictive injury / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Gabapentin has been widely and successfully used in the clinic for many neuropathic pain syndromes since last decade, however its analgesic mechanisms are still elusive. Our study was to investigate whether Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) contributes to the analgesic effect of gabapentin on a chronic constriction injury (CCI) model.</p><p><b>METHODS</b>Gabapentin (2%, 100 mg/kg) or saline (0.5 ml/100 g) was injected intraperitoneally 15 minutes prior to surgery and then every 12 hours from postoperative day 0 - 4 to all rats in control, sham and CCI groups. The analgesic effect of gabapentin was assessed by measuring mechanical allodynia and thermal hyperalgesia of rats. Expression and activation of CaMKII were quantified by reverse-transcriptional polymerase chain reaction and Western blotting.</p><p><b>RESULTS</b>The analgesic effect of gabapentin on mechanical allodynia and thermal hyperalgesia was significant in the CCI model, with maximal reduction reached on postoperative day 8. Gabapentin decreased the expression of the total CaMKII and phosphorylated CaMKII in CCI rats.</p><p><b>CONCLUSION</b>The analgesic effect of gabapentin on CCI rats may be related to the decreased expression and phosphorylation of CaMKII in the spinal cord.</p>

Effects of ning shen ling granule and dehydroepiandrosterone on cognitive function in mice undergoing chronic mild stress / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the changes of spontaneous and cognitive behavior, and cholinergic M receptors in the brain of mice subjected to chronic mild stress (CMS), and to determine the effect of Ning Shen Ling Granule (NSL) and dehydroepiandrosterone (DHEA) on them.</p><p><b>METHODS</b>CMS model mice were established by applying stress every day for 3 consecutive weeks with 7 kinds of unforeseeable stress sources, and they were medicated for 1 week beginning at the 3rd week of modeling. The changes in behavior were determined by Morris Water Maze and spontaneous movement test, and M-receptor binding activity in cerebral cortex, hippocampus and hypothalamus were measured by radioactive ligand assay with 3H-QNB.</p><p><b>RESULTS</b>(1) The spontaneous movement in CMS model mice was significantly reduced, with the latency for searching platform in Morris Water Maze obviously prolonged (P<0.01), and these abnormal changes in behavior were improved in those treated with NSL and DHEA. (2) The binding ability of M-receptor in cerebral cortex and hippocampus of CMS mice was significantly decreased as compared with those in the control group (P<0.05), but could be restored to the normal level after intervention with NSL or DHEA.</p><p><b>CONCLUSION</b>The decline of spontaneous movement and spatial learning and memory ability could be induced in animals by chronic mild stress, and that may be related to the low activity of central cholinergic M-receptors. Both NSL and DHEA could effectively alleviate the above-mentioned changes.</p>

Evaluation of neuroprotective effects of long-term low dose hormone replacement therapy on postmenopausal women brain hippocampus using magnetic resonance scanner / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the effects of long-term low dose hormone replacement therapy (HRT) on postmenopausal women in hormone level, cognition score, hippocampus volume, and magnetic resonance spectroscopy (MRS) parameters.</p><p><b>METHODS</b>A total of 182 postmenopausal women aged 50-87 years were chosen at Peking Union Medical College Hospital and assigned to HRT group and control group. The volunteers of HRT group had taken low dose hormone [estradiol (E2) 0.5-1.0 mg and progesterone 0.5-2.0 mg, once a day] for 4-33 years. The concentrations of E2, progesterone, and testosterone were measured using enzyme-linked immunosorbent assay (ELISA). The gene types of apolipoprotein E (ApoE) were measured by polymerase chain reaction, and the subjects with susceptible genes (ApoE epsilon3/epsilon4) of Alzheimer's disease (AD) were screened. Their hippocampus volumes and MRS parameters were obtained through magnetic resonance imaging (MRI), and results in two groups were analyzed by statistical method.</p><p><b>RESULTS</b>Compared with control group, the concentrations of E2 at each age stage in HRT group were significantly higher (P < 0.05) except the 80-89 years old subgroup; yet, there were no statistical differences in the concentrations of progesterone and testosterone between the two groups. There was no obvious difference in ApoE subtypes distribution between the two groups. The results of hippocampus MRI for the subjects with susceptible genes ApoE epsilon3/epsilon4 (HRT group 14 cases, control group 11 cases) showed that the ratio of bilateral hippocampus volume to whole brain volume in HRT group (0.406 +/- 0.028) was significantly higher than control group (0.369 +/- 0.031, P < 0.05). The results of 1H MRS for the subjects with susceptible genes ApoE epsilon3/epsilon4 (HRT group 12 cases, control group 11 cases) showed that the N-acetylaspartate/total creatine at the area of hippocampus in HRT group (1.54 +/- 0.08) were significantly higher than control group (1.45 +/- 0.13, P < 0.05).</p><p><b>CONCLUSIONS</b>For postmenopausal women, long-term low dose HRT can maintain the physiological concentration of E2 in plasma. Furthermore, the hippocampus MRI performed on those with ApoE epsilon3/epsilon4 genes shows that long-term low dose HRT can prevent hippocampus atrophy, which is beneficial to maintain the brain function and prevent AD.</p>

Effects of acidic oligose on differentially expressed genes in the mice model of Alzheimer's disease by microarray / 药学学报

<p><b>AIM</b>To investigate the molecular mechanism of protective effect of acidic oligose 971 on Alzheimer's disease mouse model by using microarray.</p><p><b>METHODS</b>Balb/c mice were randomly divided into control group, beta-AP(25-35) i.c.v. injected group and 971-treated group. The learning-memory ability of mice was tested by Morris water maze experiment. Total RNA of the cerebral cortex was extracted from the mice of each group. cDNA microarrays containing 1176 genes were used to investigate the gene expression pattern of each group. Expressions of 5 genes were randomly selected for further confirmation by RT-PCR.</p><p><b>RESULTS</b>Icv injection of beta-AP(25-35) caused significant impairments in spatial and working memory performances of mice in Morris water maze and which were relieved by the treatment of 971. Up- and down- regulated genes were 19 and 12 in beta-AP(25-35)-injected group vs control group, respectively. Up- and down- regulated genes were 13 and 4, respectively, in 971-treated group vs beta-AP(25-35)-injected group. RT-PCR results indicated that 5 genes showed identical results to that of the microarray.</p><p><b>CONCLUSION</b>The protective effect of 971 on learning and memory ability of beta-AP(25-35)-treated mouse may be related to the expression changes of genes involved in cell cycle, DNA repair, nerve growth, synaptic plasticity and immune response, etc.</p>

Protective effect of tetramethylpyrazine on learning and memory function in D-galactose-lesioned mice / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To explore the protective effect of tetramethylpyrazine (TMP) on the learning and memory function in D-galactose (D-gal)-lesioned mice.</p><p><b>METHODS</b>C57BL/6 mice were injected (s.c.) 2% D-gal for 40 days (100 mg x kg(-1) x d(-1)). Normal saline, TMP, and Huperzine A were respectively given by intragastric administration in different groups from the third week. Learning and memory ability was tested with Morris water maze for 5 days at the sixth week. After completion of behavioral test, the mice were sacrificed by decapitation. The brain was rapidly removed, and the cortex and hippocampus were separated. The superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in the cortex were determined. At the same time, the activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), the binding sites (Bmax) and the affinity (KD) of M-cholinergic receptor in the cortex, and Bmax and KD of N-methyl-D-aspartate (NMDA) receptor in the hippocampus were determined.</p><p><b>RESULTS</b>In this model group, (1) The deficit of learning and memory ability, (2) elevated MDA content and lowered SOD activity, (3) decreased AChE activity and M-cholinergic receptor binding sites in the cortex, and (4) lowered NMDA receptor binding sites were observed in the hippocampus, as compared with the normal control. TMP could markedly (1) attenuate cognitive dysfunction, (2) lower MDA content and elevate SOD activity, (3) increase the activity of ChAT and AChE, and M-cholinergic receptor binding sites in the cortex in the mice treated with D-gal. NMDA receptor binding sites were also increased in the hippocampus in the treated mice.</p><p><b>CONCLUSION</b>TMP can significantly strengthen antioxidative function, improve central cholinergic system function, protect NMDA receptor activity, and thus enhance the learning and memory ability in D-gal-lesioned mice.</p>

Effect of Tujian decoction on protein kinase C activity in renal cortex in diabetic rat / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate influence of administration of Tujian decoction (Chinese herbal medicine) on protein kinase C (PKC) activity, renal function and structure in diabetic rat kidney.</p><p><b>METHOD</b>Experimental diabetic nephropathy model was induced by nephrectomy combined with streptozotocin (STZ) injection in sprague-dawley rat. Tujian decoction (20 g x kg(-1) x d(-1)) and Valsartan (20 mg x kg(-1) x d(-1)) were orally administrated respectively for 12 weeks. PKC activity was measured by [3H]phorbol 12, 13-dibutyrate ([3H]PDBu) binding assay. 24 h urine protein excretion (Upro) and renal pathological changes were observed.</p><p><b>RESULT</b>In 12th week, diabetic nephrectomized rats developed proteinuria, glomerulosclerosis, increased membrane PKC activity (mPKC), decreased cytosol PKC (cPKC), and increased ratio of mPKC and cPKC (M/C). Administration of Tujian decoction or Valsartan led to a reduction in proteinuria, structural injury, mPKC and M/C, and a recovery in cPKC.</p><p><b>CONCLUSION</b>Tujian decoction possesses a renoprotective effect on diabetic nephrectomized rat, at least partially via the inhibition of PKC activation in renal cortex.</p>

Jiuqiang Naoliqing enhancing the expression of CGRP and Synapsin Ⅰ in brain of spontaneous hypertension rats / 中国康复理论与实践

@#ObjectiveTo study the influence of Jiuqiang Naoliqing (JNQ) on the expression of calcitonin gene related peptide(CGRP)and Synapsin Ⅰ in brain of the spontaneous hypertension rats (SHR). MethodsThe rats were randomly divided into 4 groups: Wistar group, SHR group, lower dose of JNQ treated SHR group and higher dose of JNQ treated SHR group. The expression of CGRP and Synapsin Ⅰ in the dentate gyrus, CA1 subfield of hippocampus and cortex were determined by immunohistochemistry after treatment for 3 weeks. ResultsCompared with the Wistar group, the expression of CGRP and Synapsin Ⅰ in the dentate gyrus, CA1 subfield of hippocampus and cortex of SHR group significantly decreased. The treatment with lower dose of JNQ significantly enhanced the expression of CGRP in cortex(P<0.05 vs SHR).The treatment with higher dose of JNQ significantly enhanced not only the expression of CGRP in the dentate gyrus, CA1 subfield of hippocampus and cortex, but also that of Synapsin Ⅰ in the CA1 subfield of hippocampus selectively in comparison with SHR group. ConclusionJNQ may improve the micro circulation in brain by up regulating the expression of CGRP and enhance the modulating function of central nervous system by up regulating the expression of Synapsin Ⅰ in spontaneous hypertension rats.

Effect of Jiuqiang Naoliqing on the TXA_2 and PGI_2 level in spontaneous hypertension rat plasma / 中国康复理论与实践

@#ObjectiveTo investigate the effect of Jiuqiang Naoliqing(JNQ) on the TXA2 and PGI2 level in spontaneous hypertension rat (SHR) plasma.MethodsThe plasma was separated after the SHR and Wistar rats were treated with JNQ at the dose of 0.133g/kg,0.265g/kg,0.530g/kg and 1% carboxymethyl cellulose respectively for 5 weeks. The level of TXB2 and 6 keto PGF1α ,stable metabolin of TXA2 and PGI 2,in SHR plasma was tested by radioimmunoassay.ResultsThe level of TXB2 and the ratio of TXB2/6 keto PGF1α (T/P) in SHR plasma increased significantly(P<0.01),and there was no significant difference in the concentration of 6 keto PGF1α between Wistar rats and SHR plasma(P>0.05). JNQ could increase the generation of 6 keto PGF1α and decrease the level of TXB2 and T/P in SHR plasma after treated with different dosages for 5 weeks.ConclusionJNQ may improve the balance between TXA2 and PGI2 in SHR plasma.

Jiuqiang Naoliqing affords protection to vital organs of spontaneous hypertension rats / 中国康复理论与实践

@#ObjectiveTo investigate the Jiuqiang Naoliqing's (JNQ) histological influence on hearts, brains and kidneys of spontaneous hypertension rats (SHR). MethodsThe rats were randomly divided into four groups: Wistar control group, SHR group, higher dose JNQ treated SHR group(0.530 g/kg) and lower dose JNQ treated SHR group(0.265 g/kg). The treatment lasted five weeks, and the rats' blood pressure were monitored through tail pulse. After the perfusion procedure, rats' hearts, brains and kidneys were rapidly removed in low temperature condition and stored in 10% formalin solution of 4 ℃.Then routine sections were obtained and the slides were stained with HE.ResultsBefore treatment, the blood pressure of SHR groups were distinctly higher than that of the control group(P<0.01), nevertheless, no obvious blood pressure downgrade were observed after three week and five week treatment. Histopathologic study showed: in SHR group,heart with hypertrophic cardiac muscle, proliferative arterial wall and strictured lumina; Cortex with angiostenosis, proliferative vascular wall and large perivascular space; Glomerulus atrophy with hyaline degeneration. These pathologic changes got respective alleviation after five week treatment of JNQ, particularly in higher dose group.ConclusionSHR who got five week treatment of JNQ didn't gain obvious blood pressure downgrade. But the treatment did good to their vital organs and can obviously alleviate hearts, brains and kidneys' pathologic changes.

Effect of Ningshen Ling and dehydroepiandrosterone on the cognitive function in mice subjected to chronic mild stress / 中国康复理论与实践

@#ObjectiveTo investigate the alteration of behavior,such as spontaneous movement,spatial memory ability and cholinergic M receptors in the brain of mice subjected to chronic mild stress (CMS). And to determine whether Ningshen Ling (NSL)and dehydroepiandrosterone(DHEA)could reverse the cognitive impairment in this model.MethodsForty mice were divided into four groups: control group,CMS group,CMS+NSL(p.o.5g·kg-1·d-1) group and CMS+DHEA (i.p.5 mg·kg-1·d-1) group. Morris water maze procedure was used to determine the spatial memory ability. M receptor binding activity was measured with radioactivity assay by3 H-QNB.ResultsAfter 3 weeks CMS,the mice exerted a decrease in spontaneous movement test,and the latency in Morris water maze was obviously prolonged. Treating CMS mice with NSL and DHEA for 1 weeks could improve the spontaneous movement and latency declined. Whereas the3 H-QNB binding ability to M receptor showed a significantly decrease in cerebral cortex and hippocampus of CMS mice (P<0.05),the decreased ability of M receptor binding was reversed by NSL treatment in hippocampus(P<0.05).ConclusionNSL and DHEA can alleviate the stress response and reversed cognitive impairment induced by CMS,and it may be concerned with the central cholinergic M receptors activity.

Effects of 7-oxo-DHEA treatment on the immunoreactivity of BALB/c mice subjected to chronic mild stress / 药学学报

<p><b>AIM</b>To determine whether 7-oxo-dehydroepiandrosterone (7-oxo-DHEA) can reverse the hypoimmunity in BALB/c mice exposed to chronic mild stress.</p><p><b>METHODS</b>A chronic mild stress animal model was established by subjecting BALB/c mice to a stressful regimen arranged in an unpredicted manner for 4 consecutive weeks. Immunological function alternations under chronic mild stress were assessed by lymphocytes proliferative response to mitogens and NK cell lysis activity test.</p><p><b>RESULTS</b>The studies showed the correlation between the state of depression and abnormalities in the immune response, such as a decrease of T lymphocytes proliferative response to Con A and suppression of cytotoxic of NK cell. Meanwhile, significant decrease of T3 and T4 levels was also observed. When stressed mice were daily given 7-oxo-DHEA 15 mg.kg-1, lymphocyte proliferative response and the NK cell activity were significantly enhanced and the decreased levels of T3 and T4 were restored in the stressed mice.</p><p><b>CONCLUSION</b>7-oxo-DHEA can improve the depressive symptoms and hypoimmunity of BALB/c mice induced by chronic mild stress as its parent DHEA.</p>

Effect of tetramethylpyrazine on learning, memory and cholinergic system in D-galactose-lesioned mice / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the effect of tetramethylpyrazine on learning, memory, and cholinergic system in D-galactose-lesioned mice.</p><p><b>METHODS</b>C57BL/6J mice were given subcutaneous injection of 2% D-galactose for 40 days (100 mg.kg-1.d-1). Normal saline, tetramethylpyrazine (TMP) and Huperzine A (HupA) were given respectively by intragastric administration in different study groups from the third week on. Learning and memory ability were tested by Morris water maze for 5 days at the sixth week. Acetylcholinesterase (AchE) activity, the binding sites (Bmax) and the affinity (KD) of M-cholinergic receptor were determined.</p><p><b>RESULTS</b>The learning and memory dysfunction, with lowered AchE activity and M-cholinergic receptor binding sites were found in the model group as compared with the normal control group. The tetramethylpyrazine, especially at the dose of 100 mg.kg-1.d-1, could markedly attenuate cognitive dysfunction, while elevate the lowered AchE activity (P < 0.05) and M-cholinergic receptor binding sites (P < 0.005) in the cerebral cortex of mice treated with D-galactose.</p><p><b>CONCLUSIONS</b>The tetramethylpyrazine can significantly improve central cholinergic system function, and thus enhance the learning and memory ability in D-galactose-lesioned mice.</p>