排钱草总生物碱对免疫性肝纤维化大鼠Ⅰ、Ⅲ、Ⅳ型胶原及TGF-β_1表达的影响

Effects of Desmodium pulchellum(L.) Benth Total Alkaloids on Type Ⅰ,Ⅲ,Ⅳ Collagens and TGF-β_1 in Rats with Immunity Hepatic Fibrosis

目的 :观察排钱草总生物碱对免疫性肝纤维化大鼠肝脏胶原沉积和转化生长因子 β1(TGF β1)表达的影响 ,研究其对肝纤维化形成的抑制作用 ,并探讨可能的作用机制。方法 :设立模型对照组、药物对照组、排钱草总生物碱高、中、低剂量组和正常对照组 ,以腹腔注射猪血清方法诱导大鼠肝纤维化动物模型。排钱草总生物碱高、中、低剂量组大鼠在注射猪血清的同时分别灌服排钱草总生物碱 3 0mg/kg ,2 0mg/kg ,10mg/kg ,1次 /d ,共 8周。大鼠肝脏HE染色 ,观察各组大鼠肝组织的炎性坏死与胶原纤维沉积变化 ;免疫组化观察大鼠肝纤维化形成过程中腓钱草总生物碱对肝脏表达Ⅰ、Ⅲ、Ⅳ型胶原蛋白及TGF β1的影响。结果 :与正常对照组比较 ,模型组大鼠肝脏出现典型的肝纤维化表现 ,肝脏胶原纤维间隔广泛形成 ,肝小叶与肝窦内胶原增生沉积明显 ,Ⅰ ,Ⅲ ,Ⅳ型胶原 (1. 2 8± 2 .5 9vs13 .82± 6. 5 5 ,1 .0 0± 1. 2 2vs 14. 69± 7 .16,1 0 3± 1 46vs 12. 44± 6/ 89,P值均 <0 . 0 0 1)及TGF β1表达明显增多。高、中、低剂量排钱草总生物碱均可以明显减轻大鼠肝脏内胶原纤维增生沉积 (P <0 . 0 5 ) ,抑制肝脏Ⅰ ,Ⅲ ,Ⅳ型胶原蛋白 (P值均 <0 0 5 )及TGF β1的合成表达。结论

Objective:To observe the effect of total alkaloids of Desmodium pulchellum on collagen deposition and express of TGF β 1 in mouse liver which were made into immunity hepatic fibrosis model, study the action of restraining hepatic fibrosis and probable effective mechanism.Methods:bo mouse were diveded into model group, positive contrast group, normal contrast group and alkaloid groups of high, medium and low concentration. Injecting pig serum into mouse abdominal cavity to induce hepatic fibrosis model. At the same time, alkaloid groups of high, medium and low concentration were given total alkaloid of Desmodium pulchellum at does of 30mg/kg, 20mg/kg and 10mg/kg respectively for eight weeks. After liver tissue was dyed into HE, the necrotic degree of liver tissue and deposition change of collagen fibre. were observed. The express of collagen protein(Ⅰ,Ⅲ,Ⅳ)and the effect on TGF β 1 were observed by immunohisto chemistry.Results:Comparing with the normal contract group, the model group had shown typical hepatic fibrosis. The interval of collagen fibre had been formed extensively. Collagen in lobules of liver and hepatic sinusoid haven grown up and deposited obviously. The number of collagen(Ⅰ,Ⅲ,Ⅳ)were 1 28±2 59,1 00±1 22 and 1 03±1 46 while those of model group were 13 82±6 55,14 69±7 16 and 12 44±6 89,so the number of P in statistics was lower than 0 001. The express of TGF β 1 increased obviously. Alkaloid groups could alleviate collagen hyperplasia and deposition obviously in liver( P <0 05) and restrain the express of collagen protein(Ⅰ,Ⅲ,Ⅳ) ( P <0 05) and synthesis of TGF β 1.Conclusion: Total alkaloid of Desmodium pulchellum can restrain collagen protein(Ⅰ,Ⅲ,Ⅳ)and synthesis of TGF β 1 for hepatic fibrosis in mouse liver amd therefore.