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目的:观察丹参粉针剂对肝纤维化大鼠肝损伤的保护作用及对血管紧张素1-7[Ang(1-7)]的影响。方法:选择成年雄性Wistar大鼠72只,随机选取16只作为空白对照组,余56只制备四氯化碳诱导的肝纤维化大鼠模型,建模成功后将肝纤维化大鼠随机分为模型组、阳性组和丹参粉针剂大剂量组、中剂量组、小剂量组,每组10只,阳性组给予重组人干扰素α2b注射液治疗,丹参粉针剂各剂量组分别给予200 mg·kg~(-1)、100 mg·kg~(-1)、50 mg·kg~(-1)丹参粉针剂治疗,空白组和模型组给予等体积的生理盐水。70 d后,评价各大鼠肝脏指数、脾脏指数、肝纤维化评分;检测大鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、谷氨酰转肽酶(GGTP)、透明质酸酶(HA)、层粘连蛋白(LN)、III型前胶原(PCIII)、IV型胶原(CIV);检测大鼠肝组织血管紧张素Ⅱ(AngⅡ)、Ang(1-7)的含量和超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)的活性。结果:1与空白组对比,模型组的纤维化评分、肝脏指数和脾脏指数均明显升高,血清中ALT、AST、GGT、HA、LN、PCIII、CIV水平显著升高,肝组织中SOD和GSH-Px水平显著降低,MDA显著升高,差异具有统计学意义(P<0.01);2与模型组对比,丹参粉针剂大剂量组、中剂量组的纤维化评分、肝脏指数和脾脏指数明显降低(P<0.01);3与模型组对比,丹参粉针剂各剂量组大鼠ALT、AST、GGT、MDA水平显著降低(P<0.05或P<0.01);SOD和GSH-Px水平显著升高(P<0.05或P<0.01),丹参粉针剂大剂量组和中剂量组大鼠HA、LN、PCIII、CIV水平显著降低(P<0.01);4与空白组比较,模型组的大鼠肝组织中AngⅡ、Ang(1-7)水平显著升高(P<0.01);与模型组对比,丹参粉针剂各剂量组的大鼠肝组织中AngⅡ显著降低,Ang(1-7)显著升高(P<0.01);丹参粉针剂大剂量组的大鼠肝组织中AngⅡ较阳性组降低,Ang(1-7)较阳性组升高(P<0.05)。结论:丹参粉针剂具有抗肝纤维化和保护肝损伤的作用,其机制可能与上调血管紧张素(1-7)各组分表达有关。
Objective: To observe the protective effects of Salvia Miltiorrhiza on hepatic injury in rats with hepatic fibrosis and its effect on angiotensin 1-7 [Ang (1-7)]. Methods: Seventy-two adult male Wistar rats were randomly divided into control group (n = 16) and control group (n = 56). C57BL / 6 rat liver fibrosis induced by carbon tetrachloride The model group, the positive group and the Salvia miltiorrhiza injection high dose group, medium dose group, low dose group, each group of 10, the positive group given recombinant human interferon α2b injection treatment, Salvia powder injection dose groups were given 200 mg · kg (-1), 100 mg · kg ~ (-1), 50 mg · kg ~ (-1) Salvia miltiorrhiza injection, and the blank group and model group were given equal volume of saline. After 70 days, the liver index, spleen index and hepatic fibrosis score of each rat were evaluated. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyl transpeptidase (GGTP), hyaluronidase (HA), laminin (LN), type III procollagen (PCIII) and type IV collagen (CIV) were measured. Angiotensin II -7) and the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were measured. Results: 1 Compared with the blank group, the fibrosis score, liver index and spleen index of the model group were significantly increased, the levels of ALT, AST, GGT, HA, LN, PCIII and CIV in the model group were significantly increased, (P <0.01) .2 Compared with the model group, the fibrosis score, liver index and spleen index of the high-dose and middle-dose Dan-shen injection groups were significantly higher than those of the model group (P <0.01 or P <0.01) .3 Compared with the model group, the levels of ALT, AST, GGT and MDA in the Salvia miltiorrhiza powder injection group were significantly decreased (P <0.05 or P <0.01); the levels of SOD and GSH-Px were significantly increased (P <0.05 or P <0.01). The levels of HA, LN, PCIII and CIV in the high-dose and medium-dose groups of Danshen powder injection were significantly decreased (P <0.01) .4 Compared with the blank group, Compared with the model group, the Ang Ⅱ and Ang (1-7) levels in the liver of the rats in each dose of Danshen powder injection were significantly decreased (P <0.01) (P <0.01). Compared with the positive group, the Ang Ⅱ level in the high-dose Danshen powder injection group was lower than that in the positive group and Ang (1-7) was higher than that in the positive group (P <0.05). Conclusion: Salvia miltiorrhiza injection can prevent liver fibrosis and protect hepatic injury. The mechanism may be related to the up-regulation of the expression of angiotensin (1-7).