丹参粉针剂对异丙肾上腺素致心肌纤维化的影响  

Salvia miltiorrhiza injectional powder attenuates isoproterenol-induced myocardial fibrosis

作　　者：许嘉旻[1] 孙懿[1] 赵欣[1] 蒲小平[1] 

机构地区：[1]北京大学药学院分子与细胞药理学系,北京100191

出　　处：《中国新药杂志》2015年第17期2010-2016,共7页Chinese Journal of New Drugs

摘　　要：目的:探讨丹参粉针剂对异丙肾上腺素致小鼠心肌纤维化的治疗作用。方法:昆明小鼠,随机分为正常组、模型组、依那普利阳性药组(2.6 mg·kg-1)、丹参粉针剂低、中、高剂量组(25,50,100 mg·kg-1),腹腔注射异丙肾上腺素50 mg·kg-1·12 h-1造模,持续15 d,各给药物组在造模的同时腹腔注射丹参粉针剂及灌胃给予阳性药20 d。实验结束后,检测小鼠心脏指数(HWI)、血清中乳酸脱氢酶(LDH)水平、心脏组织羟脯氨酸(Hyp)含量,用HE,Masson和VG染色分析小鼠心脏组织的病理变化以及结缔组织和胶原的沉积情况。结合图形软件测定VG染色中心肌胶原体积比例(CVF),用免疫组化法检测心肌中α-平滑肌肌动蛋白(α-SMA)、转化生长因子β1(TGF-β1)的表达情况。结果:与模型组比较,丹参粉针剂高剂量组的HWI和LDH显著性降低(P<0.05);中剂量组和高剂量组Hyp含量和CVF显著性降低(P<0.05或P<0.01);HE染色中心肌组织排列更整齐,肌细胞坏死减少,炎症细胞浸润减少;Masson染色显示结缔组织减少;免疫组化显示α-SMA,TGF-β1表达均有减少。结论:丹参粉针剂治疗有抗异丙肾上腺素造成的心肌纤维化作用,其机制和抑制成纤维细胞的活化,减少TGF-β1的表达有关。Objective： To determine the effects of Salvia miltiorrhiza injectional powder on isoproterenol-induced myocardial fibrosis in mice. Methods： KM mice were randomly divided into normal,model,positive control and three doses of Salvia miltiorrhiza injectional powder groups. Except for those in normal group,the mice were administered isoproterenol（ ISO）（ 50 mg·kg- 1·12 h- 1）,a selective β-AR agonist,for 15 consecutive days.Meanwhile,the positive control group was given enalapril（ 2. 6 mg·kg- 1） by gavage and the Salvia miltiorrhiza injectional powder groups were given Salvia miltiorrhiza injectional powder（ 25,50 and 100 mg·kg- 1） by intraperitoneal injection for 20 consecutive days. At the end of the experiment,all of the mice were sacrificed to remove the myocardial tissues and get the blood samples. The serum lactic dehydrogenase（ LDH） level and heart weight index（ heart weight/body weight） were determined. The myocardial fibrogenesis as well as the myocardial injury were observed by hematoxylin-eosin（ HE）,Masson trichrome and VG staining. The myocardial collagen volume（ CVF）in VG staining was estimated by using image-pro plus software. The expression levels of α-SMA and TGF-β1 were examined by immunohistochemical test. The level of hydroxyproline（ Hyp） in heart tissues was also measured. Results： After treatment with the moderate and high doses of Salvia miltiorrhiza injectional powder（ 50,100 mg·kg- 1）,the Hyp and CVF were markedly decreased（ P 0. 05 or P 0. 01） compared with the model group. The levels of LDH and HWI were decreased significantly only in the high dose Salvia miltiorrhiza injectional powder group（ P 0. 05） compared with the model group. The immunohistochemical examination showed that treatmentwith the moderate and high doses of Salvia miltiorrhiza injectional powder inhibited the expression of α-SMA which is a sign of cardiac fibroblasts＇ activation and TGF-β1 induced by ISO which plays a key role in myocardial fibrogenesis. Conclu

关 键 词：丹参粉针剂 异丙肾上腺素 心肌纤维化 胶原 转化生长因子Β1 

分 类 号：R972[医药卫生—药品]