Anti-sepsis effect and mechanism of Apocynum leavesbased on network pharmacology / 西安交通大学学报(医学版)

【Objective】 To study the mechanism of Apocynum leaves in the treatment of sepsis by network pharmacology method in order to explore the multi-dimensional research method of Xinjiang ethnic medicine treatment of infectious diseases and provide scientific theoretical basis for clinical medication. 【Methods】 TCMSP and literature collection were used to screen the main active components of Apocynum venetum leaf, and target prediction analysis was conducted by SwissTarget Prediction database. We used Genecards database to screen relevant targets for sepsis, used Omicshare to calculate Venn figure of the intersection targets, constructed the protein-protein interaction network diagram in the STRING database, used Ensembl for name conversion of protein targets, then entered Omicshare server for Go function and KEGG pathway enrichment of dynamic analysis. Last we used Cytoscape3.6.0 software to construct "Apocynum venetum leaf-the active ingredients-targets-Go-KEGG-sepsis" network to explore the mechanism of action of Apocynum’s resistance to sepsis. 【Results】 Kaferol, luteolin, proanthocyanidin B1 and phytosterol in Apocynum venetum leaves may treat sepsis by controlling signal transduction, regulating hormone level and anti-infection through predictive biological targets such as Akt1, VEGFA, MAPK3, EGFR, Src and PTGS2. They can play an important role through VEGF, EGFR, erbB, HIF-1, RAS and other enrichment pathways. 【Conclusion】 The active components of Apocynum venetum leaves can fight against sepsis through multiple targets and multiple pathways.

Relationship between TGF-β 3/Smad3 signaling pathway and neuronal apoptosis during reduction of focal cerebral ischemia-reperfusion injury by isoflurane postconditioning in rats / 中华麻醉学杂志

Objective:To evaluate the relationship between transforming growth factor beta-3 (TGF-β 3)/mammalian homologs of the drosophila mad gene 3 (Smad3) signaling pathway and neuronal apoptosis during reduction of focal cerebral ischemia-reperfusion (I/R) injury by isoflurane postconditioning (ISO) in rats. Methods:Sixty clean-grade healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 210-230 g, were randomly divided into 5 groups ( n=12 each): sham operation group (group S), cerebral I/R group (group I/R), cerebral I/R plus isoflurane postconditioning group (group I/R+ ISO), cerebral I/R plus pirfenidone group (group I/R+ P), and cerebral I/R plus isoflurane postconditioning plus pirfenidone group (group I/R+ ISO+ P). Local cerebral I/R was produced by middle cerebral artery occlusion for 1.5 h followed by 24-h reperfusion in anesthetized rats.Pirfenidone 5 μg/kg was injected into the lateral ventricle at 30 min before ischemia in I/R+ P and I/R+ ISO+ P groups.In I/R+ ISO and I/R+ ISO+ P groups, 1.5% isoflurane was inhaled for 1 h starting from the time point immediately after onset of reperfusion.Neuro-functional deficit was assessed using neurologic deficit scores (NDS) at the end of reperfusion.Then the animals were sacrificed, and brain tissues were removed for determination of the neuronal damage rate (by Nissl staining), neuronal apoptosis rate (by TUNEL), expression of TGF-β 3 (using immunofluorescence), and expression of TGF-β 3, phosphorylated Smad3 (p-Smad3), caspase-3, Bax and Bcl-2 (by Western blot). Results:Compared with group S, the NDS, neuronal damage rate and apoptosis rate of neurons were significantly increased, the expression of TGF-β 3, caspase-3 and Bax was up-regulated, and the expression of p-Smad3 and Bcl-2 was down-regulated in group I/R ( P<0.05). Compared with group I/R, the NDS, neuronal damage rate and apoptosis rate of neurons were significantly decreased, the expression of TGF-β 3, p-Smad3 and Bcl-2 was up-regulated, and the expression of caspase-3 and Bax was down-regulated in group I/R+ ISO, and the NDS, neuronal damage rate and apoptosis rate of neurons were significantly increased, the expression of TGF-β 3 and p-Smad3 was down-regulated, and the expression of caspase-3 was up-regulated in group I/R+ P ( P<0.05). Compared with group I/R+ ISO, the NDS, neuronal damage rate and apoptosis rate of neurons were significantly increased, the expression of TGF-β 3, p-Smad3 and Bcl-2 was down-regulated, and the expression of caspase-3 and Bax was up-regulated in group I/R+ ISO+ P ( P<0.05). Conclusion:Isoflurane postconditioning can inhibit neuronal apoptosis by activating the TGF-β 3/Smad3 signaling pathway, thus reducing focal I/R injury in rats.

Changes of BKCa on vascular striaepericytes of D-galactose-induced aging model in guinea pigs / 中华耳鼻咽喉头颈外科杂志

Objective@#The aging model of guinea pigs induced by D-galactose was set up to investigate the changes of BKCa expression and function on cochlear pericytes and their relationship with age-related hearing loss.@*Methods@#Thirty healthy 8-week-old guinea pigs were randomly divided into three groups, with 10 in each group: D-galactose aging model group, subcutaneous injection of D-galactose (500 mg/kg) daily for 6 weeks; saline control group, the same amount of saline was injected into the neck of the aging model group for 6 weeks; the blank control group, no treatment was performed. The threshold of auditory brainstem response (ABR) was detected. The content of BKCa in the perivascular cells of the guinea pig cochlear cells was detected by immunofluorescence technique. The changes of peripheral current density and BKCa current were detected by patch clamp technique. The data were analyzed by GraphPad Prism software.@*Results@#Compared with the saline group and the control group, the ABR threshold and the amplitude of the wave I were significantly decreased in the aging model group, and the difference was statistically significant (P<0.01). Compared with the control group, the expression of BKCa in the vascular pericytes of guinea pigs in the aging model group was significantly reduced (1.00±0.08 vs 0.27±0.03,the difference was statistically significant P<0.01), and the cell current density and BKCa net current value were also significantly reduced with statistically significant (P<0.01).@*Conclusions@#D-galactose can successfully induce guinea pig aging model, in which BKCa expression decreases and net current value decreases in pericytes of cochlear striavascularis, and changes in BKCa expression and function may be related to age-related hearing loss.

Research on clinical practice skills training system based on clinical practice ability / 中华医学教育探索杂志

Clinical medicine is a practical, highly skilled natural science. Solid clinical skills are the cornerstone of medical students' growth and development. According to the change of medical education environment, the tension of doctor-patient relationship and the lack of practical ability, we build a set allround , systematic clinical practice teaching system based on practice curriculum teaching , centralized practice teaching, social practice teaching, practice skills assessment and practice skills competition. The research and practice of the system not only promotes teachers' and student's emphasis on the training of clinical practical skills but also improves student's clinical practice skills, strengthen teachers' clinical skills teaching ability, and boost the construction of clinical skills experimental center.

Effect of calcium-sensitive receptor on intracellular Ca2+ concentration in pulmonary arterial smooth muscle cells of hypoxia-induced persistent pulmonary hypertension in mice / 中国新生儿科杂志

Objective To study the changes of intracellular calcium ion concentration in pulmonary artery smooth muscle cells (PASMCs) of hypoxic-induced persistent pulmonary hypertension (PPH) induced by calcium-sensitive receptor (CaSR) in a newborn mouse model.Method Ninety-six newbom C57BL/6 mice were randomly divided into control group,PPH group,PPH + agonist group and PPH + inhibitor group,with 24 mice in each group.The PPH model was induced by 12％ oxygen for 14 days.In the beginning,intraperitoneal injection of CaSR agonist (GdCl3) and CaSR inhibitor (NPS2390) were performed to mice in PPH + agonist group and PPH + inhibitor group respectively daily.After 14 days of modeling,pulmonary artery smooth muscle cells (PASMCs) of all four groups were cultured in vitro.Changes of Ca2+ fluorescence intensity in PASMCs of the four groups were detected by laser confocal microscope continuously.Result The ratio of pulmonary small vascular wall thickness to the vascular diameter and right ventricle/left ventricular thickness in PPH group were greater than those in the control group [(21.1％ ±1.8％) vs.(27.0％ ±0.9％),(0.62 ±0.22) vs.(0.83±0.45)],the differences were statistically significant (P ＜ 0.05),which imply that PPH mouse model was constructed successfully.The average Ca2+ fluorescence intensity in PASMCs of control group,PPH group,PPH + agonist group and PPH+ antagonist group were 122.5 ± 3.0,2 058.8 ±46.3,2 286.6 ±51.4 and 1 134.8 ± 8.5,respectively.The average Ca2+ fluorescence intensity in PASMCs of the PPH group,PPH + agonist group and PPH + antagonist group was higher than that of the control group respectively,the average Ca2+ fluorescence intensity in PASMCs of PPH group was higher than that of PPH + antagonist group,the differences were statistically significant (P ＜ 0.05).Whereas the difference of average Ca2 + fluorescence intensity in PASMCs of PPH group and PPH + agonist group was of no statistical significance (P ＞ 0.05).Conclusion CaSR may be involved in the occurrence and development of hypoxic-induced PPH in neonatal mice by affecting the intracellular Ca2+ concentration in pulmonary artery smooth muscle cells.

G protein?coupled estrogen receptor reduces renal ischemia?reperfusion injury by improving diastolic function of renal interlobular artery / 中华肾脏病杂志

Objective To investigate the effect of G protein?coupled estrogen receptor (GPER) on the diastolic function of renal interlobular artery and reduce renal ischemia?reperfusion injury in rats. Methods Female ovariectomized rats were divided into control group; ischemia?reperfusion injury (IRI) group;GPER?specific agonist (G1) intervention group;GPER?specific blocker+GPER?specific agonist (G15+G1) intervention group. Histopathological examination (HE staining), renal function test and Paller score were used to identify the success of the model and the degree of kidney damage. In vitro microvascular pressure diameter measuring instrument was used to detect the relaxation and contraction activity of renal interlobular artery in each group. Immunofluorescence technique was used to observe the expression of GPER on the renal interlobular artery. Westernblotting was used to detect the expression of GPER protein in renal interlobular artery of rats in each group. The NO content was determined by a nitrate reductase method. Results Compared with IRI group, serum BUN, Scr level and Paller score in G1 intervention group were significantly decreased (all P<0.05). The systolic rate of renal interlobar artery was significantly increased [(40.76 ± 1.57)％ vs (29.78 ± 1.87)％, P<0.05]. The results of immunofluorescence showed that GPER was expressed in renal interlobular artery smooth muscle cells and endothelial cells, and the expression of IRI group was higher than that of the control group. The expression of G15+G1 intervention group was lower than that of G1 intervention group (all P<0.05). Compared with the IRI group, the NO content in the G1 intervention group increased significantly (all P<0.05). Conclusions During renal ischemia ?reperfusion injury, GPER may regulate the systolic and diastolic activity of the renal interlobar artery by increasing the content of NO, so as to alleviate the renal ischemia?reperfusion injury.

Different effects of remifentanil on basilar artery smooth muscle cells of normotensive and hypertensive rats / 临床麻醉学杂志

Objective To evaluate the effects of remifentanil (RMF)on large conductance cal-cium-activated potassium channel (BKCa)and voltage-gated potassium channel (KV)activition currents in basilar arterial smooth muscle cells (BASMCs)of normotensive and hypertensive rats. Methods Spontaneously hypertensive rats (SHR)and homologous normotensive wistar-kyoto (WKY)rats,were used in this study.BASMCs were obtained freshly by the method of enzymolysis. Six basilar artery smooth muscle cells of each rat were chosen and analyzed.Outward current ampli-tude was recorded by the whole-cell patch clamp technique.The outward current amplitude under all stimulation voltage in set of step stimulation protocol before (basal level)and after administration of RMF (3×10-7mol/L)were recorded respectively and net current was calculated (net current=cur-rent amplitude after administration-basic value).With administration by concentrations cumulative method,the current amplitude under +60 mV stimulation voltage was separately recorded before (basic value)and after application of different concentrations of RMF (10-10,10-9,10-8,10-7, 10-6,10-5mol/L),then calculated current increasing rate and the half effective concentration (EC50)of RMF increasing current amplitude in BASMCs.Another six basilar artery smooth muscle cells of each rat were chosen and given RMF (3×10-7mol/L),and separately treated with BKCa channel blocker (tetraethylammonium,TEA)and Kv channel blocker (4-aminopyridine,4-AP),and then administrated the corresponding RMF mixture.The current amplitude was recorded after each dose.Results At 0,+20,+40 and +60 mV,the net current generated by RMF on both BASMCs of rats was successively and significantly increased (P <0.05).The increment rate of outward currents in BASMCs generated by 10-10,10-9,10-8,10-7RMF successively and significantly went upward (P<0.05).Compared to WKY rats,the half-effective concentration(EC50)of RMF increas-ing the current amplitude in BASMCs of SHR significantly rose(P<0.05).Compared with the base-line,the current amplitude in BASMCs of the two kind rats was significantly increased after adminis-tration of RMF,and decreased after administration of TEA or 4-AP (P<0.05);Compared to ad-ministration of TEA or 4-AP,the current amplitude in BASMCs of the two kind rats was significantly in-creased after administration of TEA+RMF or 4-AP+RMF (P<0.05).Conclusion Bkcaand Kv currents in both BASMCs of SHR and WKY rats were activated by RMF in a voltage-dependent and dose-dependent manner,and the effect of RMF on BKCaand Kvactivition currents in BASMCs of SHR was weaker than WKY rats.

Comparison of the Therapeutic Characteristics of Anterior Hybrid Decompression and Posterior Decompression in the treatment of Multilevel Cervical Spondylotic Myelopathy / 现代生物医学进展

Objective:To compare the therapeutic characteristics of anterior hybrid decompression and posterior cervical posterior laminectomy in the treatment of multilevel cervical spondylotic myelopathy.Methods:Thirty six cases of multilevel cervical spondylotic myelopathy patients treated by anterior hybrid decompression and thirty three cases of multilevel cervical spondylotic myelopathy patients treated by posterior cervical posterior laminectomy were involved.The general information,bleeding amount,operative time,cervical curvature D value,JOA score and incidence of postoperative complications of the two groups before and after surgery were compared.Results:There was no significant difference in the general information among the two groups(P＞0.05),including age (anterior group:56.23± 7.64 years old,posterior group:55.76± 8.18 years old),sex (anterior group:22 males/14 females,posterior group:20 males/13 females),cervical curvature D value (anterior group:7.41± 3.14,posterior group:8.19± 2.74),JOA score (anterior group:9.08± 1.09 scores,posterior group:8.82± 1.26 scores),disease course (anterior group:17.24± 7.36 months,posterior group:15.75± 5.78 months) and affected segment (anterior group:3.11 ± 0.26 segments,posterior group:3.24± 0.39 segments).The the amount of bleeding in the anterior group (anterior approach:221.79± 178.02 ml,posterior group:483.07± 434.25 ml) was lower than that of the posterior group(P＜0.05).The operative time (anterior group:196.54± 51.88 mins,posterior group:175.12± 54.93 mins) was longer,but there was no significant difference (P＞0.05).The cervical curvature D value and JOA score of posterior group were increased with the extension of surgery time.However,the cervical curvature D value of posterior group was decreased,but JOA score was increased.The incidence of bone unfinished,hoarseness and cerebrospinal fluid leakage were found in the anterior group,and axial pain and C5 nerve root paralysis were found in the posterior group.But there was no significant difference in the incidence of complications between the two groups (anterior group 14.89％,posterior group:12.12％)(P＞0.05).Conclusions:Anterior hybrid decompression and posterior cervical posterior laminectomy had their own advantages in the treatment of multilevel cervical spondylotic myelopathy.,The appropriate treatment should be taken according to the condition of patients.

Effects of propofol on the expression of gap junction Cx43 in renal arteryin rats with renal ischemia reperfusion injury / 西安交通大学学报(医学版)

Objective To observe the effects of propofol intervention on renal ischemia-reperfusion injury on the expression of Cx43 in rat renal interlobar artery.Methods Male SD rats were randomly divided into control 4h and 24h groups (control), sham operation 4h and 24h groups (sham), ischemia reperfusion 4h and 24h groups (I/R), propofol 4h and 24h groups (propofol), and fat emulsion 4h and 24h groups (intralipid).Ischemia/reperfusion model was prepared by resection of right kidney and noninvasive arterial occlusion of left kidney, with renal ischemia for 45min and reperfusion for 4h or 24h depending on different group.Serum urea nitrogen (BUN) and creatinine (Cr) were detected by automatic biochemical analyzer.HE staining was used to observe the pathological changes of renal tissue.The changes of renal artery systolic and diastolic lobes were examined by pressure myographic technique.The expression of Cx43 protein in renal interlobar artery was analyzed by Western blot.Results The concentrations of serum BUN and Cr in sham group did not differ significantly from those in the blank control group.Renal HE staining showed no significant lesions;the pressure myogram of motor renal interlobar artery contraction rate showed no significant difference.The expression of Cx43 protein did not change significantly.Compared with sham operation group, the concentrations of serum BUN and Cr in ischemia-reperfusiongroup were significantly increased.HE slices kidney showed that the pathological changes of renal tissue became obvious;pressure motor indicated renal interlobar artery contraction rate was decreased;the expression of Cx43 protein was increased significantly (P<0.05).Compared with ischemia-reperfusion group, the concentrations of serum BUN and Cr in propofol group were decreased;renal HE slices showed reduced renal tissue lesions, increased renal interlobar artery contraction rate, and decreased expression of Cx43 protein (P<0.05).Conclusion Propofol can change renal ischemia-reperfusion injury by reducing the expression of Cx43 protein in vasomotor in renal interlobar artery.

Effects of estrogen on the vasomotor function of rats' renal interlobar arteries and Cx43 expression after renal ischemia-reperfusion injury / 西安交通大学学报(医学版)

Objective To investigate the effect of estrogen (E2) on the connexin43 (Cx43) expression of renal interlobar arteries after renal ischemia-reperfusion injury (I/R).Methods The experiment was carried out in vivo using an SD rat I/R model.SD rats were randomly divided into normal group,sham-operation group,I/R group,and estrogen-intervention group.The functional changes of the kidney were analyzed after 24 hours of I/R;nephridial tissue section was stained by hematoxylin-eosin (HE),and Paller scores were used to evaluate the degree of kidney damage.Pressure myography was utilized to detect the vasomotor function of renal interlobar arteries.Immunofluorescence technique,qRT-PCR and Western blot were applied to determine the expression of Cx43 in renal interlobar arteries in different groups.Results Estrogen markedly decreased the levels of Cr and BUN in the serum of I/R rats (P＜0.05),and the damage of the kidney tissue could be improved noticeably.The vasomotor rate of renal interlobar arteries was (24.80 ± 3.70)％ after I/R and (41.60 ± 3.50)％ after treatment with estrogen,which was higher than that of I/R group (P＜0.05).The expression of Cx43 was lower in renal interlobar arteries of estrogen-intervention group than that in I/R group (P＜0.01).Conclusion Estrogen may reduce vascular tension and boost dilation of the artery by inhibiting Cx43 expression and GJ function.Therefore,estrogen may attenuate the damage of I/R and improve renal function.

Expression and significance of PAR2 and TMEM16A on DRG rat modelin of neuropathic pain / 实用医学杂志

Objective To observe the expression of PAR2 and TMEM16A in the model of chronic constriction injury (CCI) in rat dorsal root ganglion (DRG) neurons,and to explore the role of it in the neuropathic pain.Methods Rats were divided into Sham operation group (Sham) and CCI group.Both groups were observed respectively to determine thermal withdrawal latency (TWL).The expression of PAR2 and TMEM16A in the dorsal root ganglion of the rat was analyzed using Western blot and immunofluorescence.Results The difference in preoperative TWL between CCI group and Sham group rats was not statistically significant (P ＜ 0.01).TWL was signifi cantly lower at all other time points after operation (P ＜ 0.01).Immunofluorescence results showed that PAR2 and TMEM16A coexisted in rat DRG neurons.Western blot results showed that,compared with Sham group,CCI group PAR2 and TMEM16A protein expression significantly increased after 7 d and 14 d (P ＜ 0.01),and the PAR2 and TMEM16A protein expression on 14 d is higher than that of 7 d (P ＜ 0.05).Conclusions Expression level of PAR2 and TMEM16A in CCI group was significantly higher than those in Sham group.The expression level of these proteins may be the cause of rat model of neuropathic pain.

Propofol relaxes mesenteric arteriole via gap junction / 临床麻醉学杂志

Objective To investigate the effects of propofol on mesenteric artery in SD rats and to observe whether the effect of propofol on the mesenteric artery relaxation is related to the gap. Methods Pressure myograph was used to examine the effect of 18β-GA and 2-APB on the relaxation induced by propofol 1×10 -7 ,3×10 -7 ,1×10 -6 ,3×10 -6 ,1 ×10 -5 ,3 ×10 -5 ,1 ×10 -4 and 3 ×10 -4 mol/L in acutely separated mesenteric arterioles of SD rat.Results The diameter of mesenteric arteri-oles were increased from (208.6±13.4)to (213.5±13.6),(21 9.7±13.2),(226.4±12.5),(234.9 ±12.3),(245.5±13.0),(267.4±1 5.2),(336.2±18.3)and (385.9 ±14.2)μm after application of 1×10 -7 ,3×10 -7 ,1 × 10 -6 ,3 × 10 -6 ,1 × 10 -5 ,3 × 10 -5 ,1 × 10 -4 and 3 × 10 -4 mol/L propofol,re-spectively.Propofol induced dilation of the rat mesenteric arterioles in a concentration-dependent man-ner (P < 0.01 ).After pretreatment with 18β-GA and 2-APB,1 × 10 -4 mol/L propofol induced dilation was absolutely decreased (P <0.01).Conclusion These results suggest that propofol relaxes mesenteric arterioles via gap junction.

Correlation analysis between KCNJ11 polymorphism and essential hypertension in Kazakh from Xinjiang / 实用医学杂志

Objective To explore the relationship between KCNJ11-E23K polymorphism and essential hypertension (EH) in Kazakh from Xinjiang. Methods PCR-RFLP method was used to test KCNJ11-E23K genotypes of Kazakh from Xinjiang,including 237 EH patients and 221 normotension (NT). Logistic regression analysis was used to analyze the risk factors associated with EH. Results The frequencies of KCNJ11-E23K genotype (EE and (EK + KK)) and allele (E and K) were 34.18%, 65.82%, 61.60% and 38.40%respectively in EH group. There was a significant difference between two groups (P < 0.05). Weight and EE genotype were risk factors affecting EH in Kazakh from Xinjiang. Individual who carried EE genotype and allele E were 2.501 and 1.388 times than (EK + KK) and allele K suffered from EH respectively. Conclusion KCNJ11-E23K polymorphism was associated with EH in Kazakh from Xinjiang.

Effects of acute hypoxia on potassium channels in spiral ganglion cells of SD rats / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>The present study was to investigate the effects of acute hypoxia on the electrophysiological properties and outward current of spiral ganglion cell (SGC).</p><p><b>METHODS</b>SGC of newborn's Sprague Dawley (SD) rats were isolated and digested, primary cultured neurons for 8 h. By perfusion with physical saline solution containing no glucose and low oxygen, SGNs model of acute hypoxia was established. The whole-cell patch clamp recording was used to clarify the effect of hypoxia on the outward currents of SGC.</p><p><b>RESULTS</b>The outward current of SGC showed characteristics of outward rectification, which contained two major components, one sensitive to the big conductance Ca²⁺-activated K⁺ channels (BKCa) which blocked by TEA, and the other could be suppressed by the KV channel blocker 4-AP. When holding at -60 mV, acute hypoxia increased the outward current of SGC in a voltage-dependent manner, which mainly increased the amplitude of the current activated by the votage ranged from 0 mV to +60 mV, and increased the amplitude of outward current from (1 160.0 ± 129.1) pA to (2 428 ± 239.3) pA (n = 9, P < 0.01) at holding potential of -60mV. By perfusion with the Potassium channel blocker TEA or 4-AP, the former could significantly reduced the increasing of outward currents induced by hypoxia on the SGC, the latter had no significant effect on the outward current increased by the hypoxia.</p><p><b>CONCLUSIONS</b>These results suggest that acute hypoxia causes neuron hyperpolarization possibly by activating big conductance BKCa of the SGC. When the BKca channels are activated, K⁺ effluxes increase, which induces cell membrane hyperpolarization, and decreases cell excitability, which may affect the conducting function of SGC.</p>

Difference expression of Cx37 and Cx40 of arteries in spontaneously hypertensive rats / 重庆医学

Objective To investigate the change of connexin (Cx) in mesenteric artery (MA) and aorta of spontaneously hyper‐tensive rats (SHR) and normotensive rats .Methods Quantitative RT‐PCR and Werstern blot technique were used to compare the difference in the expression of Cx37 and Cx40 mRNA and protein in MA and aorta of SHR and normotensive rats .Results The level of Cx37 mRNA expression in MA from SHR was decreased compared with that of the normotensive rats (P0 .05) .The expression of Cx37 protein in MA from SHR was decreased compared with that of the normotensive rats (P0 .05) . Conclusion Hypertension may could decrease gap junctional communication in cells of MA and aorta from SHR by the downregu‐lation of the expression of Cx37 and/or Cx40 .

Inhibitive effect of hypoxia on vasoconstriction of phenylephrine in mesenteric arterioles of guinea pig / 实用医学杂志

Objective To investigate the effects and mechanisms of hypoxia on the contraction of mesen-teric arteries induced by phenylephrine (PE) in guinea pig. Methods Pressure myograph system was used to study the effects of 20, 40 and 60 min hypoxia (mixed with 95% CO2 and 5% O2) on the constriction induced by PE in acutely separated mesenteric artery (300 ~ 400 μm) of guinea pig. Results PE (0.1 ~ 100 μmol/L) caused the contractions of the mesenteric arteries in guinea pig in a concentration-dependent way . Hypoxia de creased the pH value of perfusion fluid from 7.4 to 6.3. Hypoxia significantly inhibited PE-induced vasocon-striction, and the inhibition was hard to recover after reoxygenation. Hypoxia inhibited PE-induced vasoconstric-tion in a time-dependent way , with the inhibition rate reduced in the sequence of inhibition duration of 60 , 40 and 20 min. When its value was decreased to 6.3 , the perfusion fluid even inhibited PE-induced vasoconstric tion. Conclusion Hypoxia can inhibit PE-induced vasoconstriction in the mesenteric arteries of guinea pig in a time-dependent way. The mechanism may have something to do with the change of pH.

Association between KCNJ11 polymorphism and essential hypertension in Xinjiang Kazak population / 西安交通大学学报(医学版)

Objective To investigate the relationship between the single nucleotide polymorphism (SNP)of KCNJ1 1 (inwardly rectifying potassium channel,subfamily J,member 1 1)gene and essential hypertension (EH)in Xinjiang Kazak population.Methods The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP ) method was used to detect genotypes of rs2285676 polymorphism of KCNJ1 1, including 126 hypertensives (EH group)and 126 normotensives (NT group)in Xinjiang Kazak population.Multiple-factor unconditional Logistic regression analysis was used to evaluate the risk factors for hypertension in Xinjiang Kazak. Results Logistic regression analysis showed that KCNJ1 1-rs2285676 genotypes,sex,weight,total cholesterol and triglyceride were not associated with hypertension;body mass index (BMI)and high-density lipoprotein (HDL) were protective factors affecting hypertension while low-density lipoprotein (LDL ) was a risk factor for hypertension.Genotypes (TT,CT and CC)and allele frequencies (T and C)of the SNP of rs2285676 in KCNJ1 1 gene were 50.00%,48.41%,1.59%,74.21% and 25.79% in EH group,respectively.The differences between EH and normal control were not significant (P >0.05).Conclusion The rs2285676 polymorphism of KCNJ1 1 is not associated with EH in Xinjiang Kazak population.

Relationship between the Cx37 polymorphism of connexin gene and essential hypertension in Kazak and Han population in Xinjiang / 天津医药

Objective To investigate the association of the Cx37 polymorphism of connexin gene with essential hyper?tension (EHT) in Xinjiang Han and Kazak population. Methods In Xinjiang region, 500 EHT patients (EHT group) were in?cluded in this study including Kazak 250 cases and Han 250 cases. Five hundred healthy volunteers (NT) were used as NT group including Kazak 250 cases and Han 250 cases. The values of age, body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressure (DBP), and other general clinical features were compared between two groups. The poly?morphism of Cx37 gene rs1630310, rs697372 and rs705193 SNP were compared between EHT and NT groups in the two eth?nic groups. Hardy-Weinberg equilibrium was used to detect the representation, and differences of genotype frequencies and gene frequency were calculated in two groups of Kazak and Han groups. Results There were significant differences in BMI, SBP, DBP, apolipoprotein ratios and homocysteine between EHT group and NT group in Kazak and Han groups (P0.05). The differences of Kazak rs1630310 genotype and gene frequency were statistically significant (P0.05), but the difference of gene frequen?cy was statistically significant (P<0.05). There were no significant differences in rs1630310 and rs697372 locus genotype and gene frequency in two groups of Han group. Conclusion Cx37 gene polymorphism is associated with the occurrence of EHT in Xinjiang Kazak population, which may be related with the rs1630310 and rs697372 polymorphism.

Niflumic acid relaxes mesenteric small artery through downregulating connexin 43 expression in smooth muscle cells from spontaneously hypertensive rat / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the impact of niflumic acid (NFA) on connexin 43 (Cx43) expression in smooth muscle cells of mesenteric small artery from spontaneously hypertensive rats (SHR).</p><p><b>METHODS</b>Blood pressure of Wistar rats and spontaneously hypertensive rats (SHR) was measured by the tail cuff method. Relaxation and contraction of mesenteric small artery from Wistar rat and SHR were evaluated by pressure myograph system under various concentrations of NFA. Protein Cx43 expression on primary cultured mesenteric smooth muscle cells from Wistar rats and SHR was detected in the absence and presence of various NFA concentrations by Western blot.</p><p><b>RESULTS</b>Phenylephrine resulted in mesenteric small arteries contraction [(193 ± 13.5) µm], while NFA (3×10(-4) mol/L) could relax the artery [(275 ± 17.1) µm]. The relaxation response in Wistar rats was significantly stronger than that in SHR (P < 0.05). Cx43 expression of the first level branch and the third branch mesenteric artery of SHR were higher than the corresponding branch vessels of Wistar rats, and the Cx43 expression of the third branches of mesenteric artery was higher than that of the first branch (F = 1 014.43, P < 0.01). Cx43 expression in primary cultured mesenteric smooth muscle cells was significantly downregulated post NFA treatment in a concentration dependent manner.</p><p><b>CONCLUSION</b>In the SHR mesenteric small arteries, Cx43 may be involved in smooth muscle cells communication, thereby affecting vascular contraction and relaxation responses.NFA could downregulate the expression of Cx43 in SHR mesenteric artery vascular smooth muscle cells and induce vasodilation.</p>

Inhibitory effects of flufenamic acid on gap junction of vascular smooth muscle cells in guinea pig / 重庆医学

Objective To investigate the influence of flufenamic acid (FFA) on gap junction intercellular communication in vascu-lar smooth muscle cells(VSMC) in situ of acutely isolated arteriole segments .Methods Whole-cell patch clamp recordings were used to study the effects of FFA on membrane input capacitance (Cinput ) ,membrane input conductance(Ginput ) or membrane input re-sistance(Rinput ) of VSMCs embedded in arteriole segments .Results FFA concentration-dependently and reversibly suppressed Ginput or increased Rinput ,with an IC50 of 56 and 33μmol/L in acutely isolated mesenteric artery(MA) and brain artery(BA) segments re-spectively .There was not significant difference between MA and BA (P> 0 .05) .After application of FFA (≥ 300 μmol/L) ,the Cinput ,Ginput and Rinput of the in situ cells were very close to the respective dispersed cell in MA and BA .Conclusion FFA is a reversi-ble gap junction blocker ,achieving a complete electrical isolation of the recorded VSMC at ≥300 μmol/L .FFA suggesting a homo-geneous property of the gap junctions between MA and BA .