Effect of Huatan Tongluo Decoction on Gut-Brain Axis in Rats with Cerebral Ischemia/Reperfusion / 中国实验方剂学杂志

Objective:To explore the effects of Huatan Tongluo Decoction （HTTLD） on the morphology and function of brain tissues and intestine in rats with cerebral ischemia/reperfusion based on the gut-brain axis. Method:Sixty SPF male rats were randomly divided into a sham operation group， a model group， high- （28.66 g·kg^-1）， medium- （14.33 g·kg^-1）， and low-dose （7.16 g·kg^-1） HTTLD groups， and an edaravone （4 g·kg^-1）+<italic>Clostridium butyricum</italic> （5.0×10⁸ cfu·mL^-1） group. The model was established by focal cerebral ischemia/reperfusion in rats. The drugs were administered by gavage. The brain tissue injury was determined by neurological deficit score and 2，3，5-triphenyl tetrazolium chloride （TTC） staining. The effect of cerebral ischemia/reperfusion on intestinal motility was assessed by the propulsion rate of small intestine. The intestinal mucosal cell damage was evaluated by the pathomorphological examination of the duodenal mucosa. Enzyme-linked immunosorbent assay （ELISA） was used to determine the content of <italic>D</italic>-lactate （<italic>D</italic>-LAC）， diamine oxidase （DAO）， and bacterial endotoxin （lipopolysaccharide， LPS） in serum. Western blot was used to detect the expression of Occludin， Claudin-5， and zonula occludens 1 （ZO-1） in the duodenum. Result:After cerebral ischemia/reperfusion， rats developed neurological deficit symptoms. The neurological deficit score in the model group was higher than that in the sham operation group （<italic>P<</italic>0.01）. Compared with the model group， the high- and medium-dose HTTLD groups could relieve the symptoms of neurological deficits and lower neurological deficit scores （<italic>P<</italic>0.01）. The results of TTC staining showed that the model group presented obvious infarcts in brain tissues compared with the sham operation group （<italic>P<</italic>0.01）. The cerebral infarction volumes of HTTLD groups were reduced compared with that in the model group （<italic>P<</italic>0.01）， especially the high-dose HTTLD group， and the effect was dose-dependent. Furthermore， the propulsion rate of small intestine in the model group was significantly reduced compared with that in the sham operation group （<italic>P<</italic>0.01）. Compared with the model group， HTTLD groups could increase propulsion rates of small intestine （<italic>P<</italic>0.01）， especially the high-dose HTTLD group， and the effect was dose-dependent. After cerebral ischemia/reperfusion， obvious duodenal mucosal damage could be observed， which was relieved after the administration of HTTLD. Western blot results showed that the protein expression of ZO-1， Occludin， and Claudin-5 in the model group was reduced compared with that in the sham operation group （<italic>P<</italic>0.01）. Compared with the model group， the HTTLD groups could up-regulate the expression of ZO-1， Occludin， and Claudin-5 to varying degrees （<italic>P<</italic>0.05， <italic>P<</italic>0.01）， especially the high-dose HTTLD group. ELISA showed that the serum <italic>D</italic>-LAC， DAO， and LPS of the model group were elevated compared with those in the sham operation group （<italic>P<</italic>0.01）. Compared with the model group， the HTTLD groups showed reduced <italic>D</italic>-LAC and DAO （<italic>P<</italic>0.05， <italic>P<</italic>0.01）， and the medium- and high-dose HTTLD groups showed reduced LPS （<italic>P<</italic>0.05， <italic>P<</italic>0.01）， especially the high-dose HTTLD group. Conclusion:After cerebral ischemia/reperfusion， the rats showed damaged brain tissues， neurological dysfunction， intestinal mucosal injury， weakened intestinal motility， and destroyed the intestinal mucosal barrier. HTTLD can protect against brain-gut axis injury after cerebral ischemia/reperfusion by reducing the damage on brain tissues and gastrointestinal mucosa， relieving the symptoms of neurological deficits， promoting gastrointestinal motility， improving intestinal barrier function， and reducing the release of intestinal bacterial metabolites or poisons.

Protective effect and mechanism of curcumin on aorta in rats with metabolic syndrome / 中国中药杂志

To investigate the protective effect and mechanism of curcumin on aorta in rats with metabolic syndrome,72 SD rats were randomly divided into blank control group,model control group,positive control group,curcumin low,middle and high dose groups.The rat model of metabolic syndrome was established in all groups except the blank control group. After the intervention by curcumin,the blood pressure,blood lipid,blood glucose,serum insulin and insulin sensitivity index were measured. The contents of serum leptin(LP),adiponectin(ADP) and tumor necrosis factor-α(TNF-α) in rat aorta were detected by enzyme-linked immunosorbent assay(ELISA),and the pathological changes of rat thoracic aorta were observed by HE staining and electron microscope scanning. Western blot assay was used to detect the expression of inducible nitric oxide synthase(i NOS) and endothelial nitric oxide synthase(e NOS) in rats. The results showed that the blood lipid level,fasting blood glucose,fasting insulin,insulin sensitivity index,systolic blood pressure,LP,TNF-α and intima/media thickness ratio in the model control group were significantly higher than those in the blank control group. As compared with the model control group,the levels of blood lipids,fasting blood glucose,fasting insulin,insulin sensitivity index,systolic blood pressure,LP,TNF-α and intima/media thickness ratio were significantly decreased in positive control group,low,middle and high dose curcumin groups. The difference was statistically significant. The results of HE staining showed that the intima of the thoracic aorta in the model group was significantly thickened; the endothelial cell membrane was wrinkled and the organelle was ruptured. The intima of the thoracic aorta in the positive control group was slightly thickened and the structure of endothelial cells was intact,with no foam cells and no abnormality in the adventitia. There was no significant thickening of the thoracic aorta in the low,middle and high dose curcumin groups,and the endothelial cells were still intact. The results of Western blot assay showed that the expression levels of i NOS and e NOS were decreased significantly in the model group,while the expression levels of i NOS and e NOS were increased significantly in the positive control group and curcumin groups. The results indicated that curcumin had a certain protective effect on the aorta of rats with metabolic syndrome and improves the aortic endothelial dysfunction,and its mechanism may be related to the fact that curcumin could reduce the production of oxygen free radicals and up-regulate the expression of i NOS and e NOS in aorta.

Effects of cardiac resynchronization therapy in patients with advanced congestive heart failure evaluated by real-time 3-dimensional echocardiography / 中华心血管病杂志

<p><b>OBJECTIVE</b>To quantitatively assess the effects of cardiac resynchronization therapy (CRT) in patients with advanced congestive heart failure by real-time 3-dimensional(3D) echocardiography (RT-3DE).</p><p><b>METHODS</b>Eighteen patients with advanced congestive heart failure underwent CRT with New York Heart association(NYHA) class III and IV and wide QRS complex (>120 ms) were included (17 dilated cardiomyopathy and 1 ischemic cardiomyopathy). Before CRT and 8 months after CRT, the clinical and RT-3DE parameters and outcome were analyzed.</p><p><b>RESULTS</b>The biventricular pacemaker was successfully implanted in 17 patients (94.4%). Compared with before CRT, NYHA class of patients decreased by 1.5 class (P < 0.01), left ventricular ejection fraction increased by 25% (P < 0.01), left ventricular end systolic volume decreased by 38% (P < 0.01), left ventricular systolic dyssynchrony index (SDI) improved significantly (14.2% before CRT vs. 9.8% after CRT, P < 0.01 ) post CRT. Change in SDI and change in LVEF was positively correlated (r = 0.62, P < 0.01) . The procedure complications and outcome during and after CRT included coronary sinus dissection (n = 1), left ventricular lead dislodgement (n = 1), phrenic nerve stimulation (n = 1), sudden cardiac death (n = 1). Three non-response patients were complicated with atrial fibrillation, nonspecific intraventricular block and dilated cardiomyopathy with postero-lateral scar tissue.</p><p><b>CONCLUSIONS</b>CRT could improve the cardiac function, correct the mechanical desynchronization and reverse left ventricular remodeling in patients with congestive heart failure, and SDI quantification by RT-3DE could predict increase of LVEF after CRT, however, there were complications related to the implantation procedure and possibilities of non-response.</p>

Efficacy and safety of tirofiban use after successful percutaneous coronary intervention for patients with moderate to high risk non-ST segment elevation acute coronary syndromes / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of tirofiban use immediately after successful percutaneous coronary intervention (PCI) in patients with moderate to high risk non-ST segment elevation acute coronary syndromes (NSTE-ACS).</p><p><b>METHODS</b>NSTE-ACS patients undergoing successful PCI (n = 246) were randomized by the envelope method to tirofiban group (n = 122, 10 µg/kg bolus within 3 min followed by 0.10-0.15 µg×kg(-1)×min(-1) for 36 h i.v.) or control group (n = 124, saline i.v. for 36 h). The primary efficacy composite end point was death, myocardial infarction, target vascular revascularization or ischemic stroke at 30 days. The second end point was the occurrence of composite end point at 7 days or 6 months. Key safety end points were bleeding and thrombocytopenia 3 days after PCI.</p><p><b>RESULTS</b>Baseline characteristics were well-balanced between the two groups (P > 0.05). The primary end point occurred in 0.9% (1/117) patients in the tirofiban group and 3.3% (4/123) patients of those in the control group (P = 0.40). There was no significant difference in the composite end point at 7 days [0.8% (1/122) vs. 3.2% (4/124), P = 0.38] between the groups, however, there was a trend towards lower composite efficacy end points at 6 months in tirofiban group compared to control group [0.9% (1/117) vs. 5.9% (7/118), P = 0.07]. The probability of survival free of composite end point was significantly higher in the tirofiban group than that in the control group (99.2% vs. 94.2%, log-rank test, P = 0.03). There was no GUSTO severe or moderate bleeding or severe thrombocytopenia within 3 days post-PCI. There was no significant difference in mild bleeding [13.1% (16/122) vs. 7.3% (9/124), P = 0.13] or mild thrombocytopenia [0.8% (1/122) vs. 0.8% (1/124), P = 1.00] between the groups.</p><p><b>CONCLUSION</b>Tirofiban use after successful PCI can improve 6-month event-free survival without increasing the risk of bleeding for patients with moderate to high risk NSTE-ACS.</p>

Angiotensin(1-7) attenuates left ventricular dysfunction and myocardial apoptosis on rat model of adriamycin-induced dilated cardiomyopathy / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effect of Angiotensin(1-7) [Ang(1-7)] on left ventricular dysfunction and myocardial apoptosis on rat model of adriamycin-induced dilated cardiomyopathy (ADR-DCM).</p><p><b>METHODS</b>Weight-matched adult male Wistar rats were randomly divided into 3 groups: (1) the ADR-DCM group (n = 25), in which 2.5 mg/kg of ADR was weekly intravenously injected for 10 weeks. (2) Ang(1-7) group (n = 25), in which ADR rats were simultaneously treated with angiotensin-(1-7) (24 µg×kg(-1)×h(-1), ip.) for 12 weeks. (3) normal control group (n = 10). Hemodynamics and echocardiography examination were performed at 12 weeks. The malondialdehyde (MDA) was measured by TBA methods. The plasma concentration of AngII was determined by immunoradiometric assay. The pathological change was analyzed by histological hematoxylin-eosin staining. Myocardial apoptosis was assessed by TUNEL method. The protein expression of pro-apoptotic protein caspase-3, Bax and anti-apoptotic protein Bcl-xl in cardiomyocytes were detected by Western blot.</p><p><b>RESULTS</b>Mortality was significantly lower in Ang(1-7) group than in ADR-DCM group (16% vs. 40%, P < 0.01). Compared to the control group, left ventricular end-diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD) and left ventricular end-diastolic pressure (LVEDP) were significantly increased in ADR-DCM group (all P < 0.01) while fractional shorting (FS), +dp/dtmax and -dp/dtmax were significantly reduced in ADR-DCM group (all P < 0.01). LVEDD, LVESD and LVEDP were significantly reduced while FS, +dp/dtmax and -dp/dtmax were significantly higher in Ang(1-7) group compared to the ADR-DCM group, but still higher than the control group (all P < 0.01). The concentrations of AngII and MDA were higher in the ADR-DCM group than in the control group (P < 0.01), which were significantly reduced by Ang(1-7) treatment (P < 0.01). The TUNEL-positive cells and apoptosis index, the expression of pro-apoptotic protein caspase-3 and Bax were significantly higher while the expression of anti-apoptotic protein Bcl-xl was significantly lower in the ADR-DCM group than in the control group (all P < 0.01) which could all be partially reversed by Ang(1-7) treatment (all P < 0.01).</p><p><b>CONCLUSION</b>Ang(1-7) could significantly attenuate left ventricular dysfunction and myocardial apoptosis in this model by downregulating pro-apoptotic protein caspase-3 and Bax and upregulating anti-apoptotic protein Bcl-xl expression.</p>