冬连三七组分改善糖尿病动脉粥样硬化兔心肌病理的机理研究

Mechanism Study of CONR Improving Myocardial Injury in DA Rabbits

目的:在既往研究冬连三七组分(Composition of Ophiopogon polysaccharide,Notoginseng total saponins and Rhizoma Coptidis alkaloids,CONR)能改善糖尿病动脉粥样硬化(diabetic atherosclerosis,DA)兔蛋白非酶糖基化基础上,探讨CONR减轻RAS系统激活,提高Na^+-K^+-ATPase活性从而保护DA兔心肌组织的机制。方法:予雄性纯种新西兰大白兔高脂饮食并静脉推注四氧嘧啶且行腹主动脉内膜球囊损伤术诱导DA模型,正常组每日给予生理盐水20 m L灌胃作为对照,实验组分别每日给予辛伐他汀3 mg/kg,CONR 450 mg/kg、150 mg/kg、50 mg/kg;灌胃10周。测定各组大兔心脏重量、左心室重量、心体比、左心室/体重指数、心肌血管紧张素Ⅱ(AngⅡ)、Na^+-K^+-ATPase含量及血管紧张素转化酶(ACE)受体在心肌组织的表达,HE染色法观察大兔心肌病理。结果:与模型组比较,CONR大中剂量组可显著降低DA大兔心脏重量、左心室重量、心体比、左心室/体重指数、心肌组织AngⅡ含量(P<0.05),升高心肌Na^+-K^+-ATPase含量(P<0.01),并抑制心肌ACE受体表达(P<0.01);明显改善了DA兔心肌细胞水肿、炎性细胞浸润、心肌间质纤维排列紊乱增生等病理改变。结论:冬连三七组分可能通过抑制蛋白非酶糖基化,减轻RAS系统激活,提高Na^+-K^+-ATPase活性从而改善DA兔的心肌损伤。

Objective： To explore the effects of the composition of Ophiopogon polysaccharide,Notoginseng total saponins and Rhizoma Coptidis alkaloids（ CONR） on myocardial injury in rabbits with diabetic atherosclerosis（ DA） by reducing RAS system activation and increasing Na＋-K＋-ATPase activity on the basis of the study that CONR improving protein non-enzymatic glycation（ PRG）. Methods： DA models were established by alloxan intravenous injection combined with the injury of abdominal aorta intima balloon. The experimental groups were daily given Simvastatin（ 3 mg/kg） and CONR（ 450 mg/kg,150 mg/kg,50 mg/kg） for 10 weeks; the control group was given saline 20 ml. The left ventricular weight（ LVW）,cardiac weight（ CW）,left ventricular/body mass index（ LC/W）,heart body ratio（ C/W）,and the expressions of myocardial angiotensin II（ Ang II）,Na＋-K＋-ATPase,angiotensin converting enzyme（ ACE） receptor in cardiac muscle tissue were detected,and myocardial pathology was observed by HE staining method. Results： Compared to the model group,CW,LVW,C/W,LC/W,and Ang II were significantly reduced（ P 0. 05）,Na＋K＋-ATPase content was significantly increased（ P 0. 01）,and the expression of myocardial ACE receptor was inhibited（ P 0. 01） in the high-dose CONR group and in the medium-dose CONR group. The improvements of swelling of myocardial cells,inflammatory cell infiltration,myocardial interstitial fiber arrangement and other pathological changes were also seen in the high-dose CONR group and in the medium-dose CONR group. Conclusion： CONR may improve myocardial injury of DA rabbit by inhibiting PRG,reducing RAS system activation and increasing Na＋K＋-ATPase activity.