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目的 研究血管紧张素Ⅱ (angiotensinⅡ )Ⅰ型受体 (AT1)拮抗剂losartan对肝硬化大鼠Ⅰ型胶原 (TypeⅠcollagencolⅠ )基因表达的影响及抗纤维化作用。 方法 4 1只雄性SD大鼠被随机分为 4组 :对照组 (10 )、模型组 (11)、及治疗组 (2 0 )———早期和中期各 10只 ,除对照组外所有大鼠均给予 5 0 %CCl4灌胃 ,3ml/(kg·5d)一次 ,共 9周。治疗组 :早期组同时给予血管紧张素受体拮抗剂losartan灌胃 ,中期组于造模中期 (5周 )开始给药 ,用量 10mg/(kg·d)至处死前。实验结束后 ,处死取肝脏液氮冻存及福尔马林固定标本 ,分别行HE及Masson染色 ,光镜下观察组织学改变 ,图像分析系统测量胶原面积。免疫组化及RT PCR检测Ⅰ型胶原蛋白及mRNA的表达。结果 光镜下组织学检查纤维化分级、图像分析系统测量胶原面积losartan治疗组低于模型组 (P <0 0 5 )。与模型组相比 ,Losartan治疗组使Ⅰ型胶原蛋白及mRNA的表达明显降低 (P <0 0 1)。结论 Losartan对CCl4诱导的大鼠肝纤维化有良好的防治作用。
Objective To investigate the effect of losartan, an angiotensin Ⅱ type 1 receptor (AT1) antagonist, on the type Ⅰcollagencol Ⅰ gene expression in cirrhotic rats and the antifibrotic effect. Method 4 One male SD rats were randomly divided into 4 groups: control group (10), model group (11), and treatment group (20) - 10 in the early and middle stages, except for the control group Rats were given 50% CCl4 gavage, 3ml / (kg · 5d) once a total of 9 weeks. In the treatment group, the losartan, an angiotensin receptor antagonist, was given to the rats in the early stage. The mid-term group was started at the mid-stage of modeling (5 weeks), and the dosage was 10 mg / (kg · d) before sacrifice. At the end of the experiment, the liver was frozen with liquid nitrogen and formalin fixed specimens were stained with HE and Masson, histological changes were observed under light microscope, image analysis system to measure the area of collagen. Immunohistochemistry and RT PCR were used to detect the expression of type Ⅰ collagen and mRNA. Results Histopathological examination of fibrosis grading by light microscopy, the image analysis system measured collagen area Losartan treatment group than the model group (P <0 05). Compared with the model group, the Losartan treatment group significantly reduced the expression of type Ⅰ collagen and mRNA (P <0.01). Conclusion Losartan has a good preventive and therapeutic effect on CCl4-induced hepatic fibrosis in rats.