膈下逐瘀汤对血瘀型非酒精性脂肪性肝炎大鼠血管内皮功能的影响

目的:观察膈下逐瘀汤对血瘀型非酒精性脂肪性肝炎(NASH)大鼠血管内皮功能的影响,探讨其防治NASH的作用机制。方法:SD大鼠随机分成正常组、模型组及膈下逐瘀汤3组,每组10只。以高脂饮食喂养联合NE加BSA复合因素造模,同时膈下逐瘀汤组每天灌服膈下逐瘀汤流浸膏14g/kg.d-1。全部大鼠于第12周末观察大鼠血瘀体征,测定大鼠血液流变学指标;化学法测定肝组织匀浆TG、CHOL含量;ELISA法检测血浆TXB2、6-Keto-PGF1α、t-PA、PAT-1、ET-1及血清NO水平;油红"O"染色及HE染色光镜下观察肝组织脂肪变和炎症程度,并进行NAFLD炎症活动度积分(NAFLD activity score,NAS)。结果:模型组大鼠血瘀体征积分、NAS、全血黏度(高、中、低切)、全血还原黏度(高、中、低切)、红细胞聚集指数和刚性指数、肝脏TG和CHOL含量、血浆TXB2、PAI-1、ET水平以及TXB2/6-Keto-PGF1α、PAI-1/tPA、ET/NO比值均较正常组明显增高,血tPA含量较正常组明显降低;应用膈下逐瘀汤干预后,大鼠血瘀体征积分值较模型组明显降低(P<0.01),肝组织的脂肪变及炎症程度明显减轻(P<0.01),全血黏度(高、中、低切)、全血还原黏度(高、中、低切)、红细胞聚集指数和刚性指数均明显降低(P<0.05、P<0.01),大鼠肝脏TG、CHOL含量明显降低(P<0.05),血TXB2、PAI-1、ET含量以及TXB2/6-Keto-PGF1α、PAI-1/tPA、ET/NO比值均明显降低(P<0.05、P<0.01),而tPA含量则明显增高(P<0.05)。结论:血瘀型NASH大鼠存在肝组织脂肪变和炎细胞浸润的脂肪性肝炎病理特征,以及中医血瘀证表现。膈下逐瘀汤调节血液流变学、改善血管内皮功能可能是其防治血瘀型NASH发展的作用机制之一。

EFFECT OF GEXIA ZHUYU DECOCTION ON VASCULAR ENDOTHELIAL FUNCTION IN BLOOD STASIS RATS WITH NONALCOHOLIC STEATOHEPATITIS

Objective:To study the effect of gexia zhuyu decoction on vascular endothelial function in blood stasis rats with nonalcoholic steatohepatitis(NASH) and explore its mechanisms of prevention and cure NASH.Methods:30 SD rats were randomly divided into three groups,normal group,model group and gexia zhyu decoction group,rats in normal group were fed with standard diet,rats in the other two groups were fed with high-fat diet and dealed with NE and BSA,meanwhile rats in the gexia zhuyu decoction group were given gexia zhuyu decoction extracts,in the end of 12th week,blood-stasis signs of rats were observed and rheology was determined,TG and CHOL contents in hepatic tissue were examined by chemical method,plasm TXB2、6-Keto-PGF1α、t-PA、PAI-1、ET-1and serum NO were detected by ELISA method,The pathological changes of liver tissue were observed by HE staining and oil red "O"staining,activity scores(NAS) were also integrated.Results:To compare with normal group,blood stasis-signs scores,NAS,the whole blood viscosity(high,middle,low),the whole blood reduced viscosity(high,middle,low),erythrocyte aggregation and index of rigidity,the contents of liver TG and CHOL,the level of TXB2,PAI-1,ET,TXB2/6-Keto-PGF1α,PAI-1/tPA,ET/NO in model group were increased significantly,the level of plasm tPA in model group was lowered.To compared with model group,the fatty degeneration,inflammatory cells infiltration of rats’ liver tissues in the gexia zhuyu decoction group were lowered(P<0.01),the blood stasis-signs scores were obviously lowered(P<0.01),the whole blood viscosity(high,middle,low),the whole blood reduced viscosity(high,middle,low),erythrocyte aggregation and index of rigidity were also lowered(P<0.05,P<0.01),the content of liver TG and CHOL became lower(P<0.05),the levels of plasm TXB2,PAI-1,ET,TXB2/6-Keto-PGF1α,PAI-1/tPA and ET/NO were lowered significantly,the level of serum tPA was increased obviously(P<0.05).Conclusion:Gexia zhuyu decoction could regulate rheology state and improve vascular endothelial function to prevent the development of blood stasis type nonalcoholic steatohepatitis.