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目的:旨在探讨丹参酮ⅡA(TanshinoneⅡA,TSN)对抗肝纤维化大鼠的作用及机制。方法:采用四氯化碳(CCl_4)诱导大鼠肝纤维化动物模型。将Wistar大鼠随机分为正常组、CCl_4模型组、阳性对照联苯双酯组(100mg/kg)、T5N高、中、低(21.3、14.2、7.1mg/kg)剂量组,药物均以灌胃的方式给药6周。治疗结束后,动物采血处死,分离血清观察TSN对慢性肝纤维化大鼠的生化指标的影响;取固定部位肝组织进行羟脯氨酸含量测定及病理组织学检查;免疫组织化学技术观察肝组织中转化生长因子(TGF-β1)及α-平滑肌动蛋白(α-SMA)的表达。结果:TSN可以降低肝纤维化大鼠血清中透明质酸(HA)、层黏素(LN)和肝组织羟脯氨酸(Hyp)的含量(P<0.05,P<0.01);HE和Masson胶原纤维特殊染色发现TSN可以改善肝纤维化的病理损伤;肝组织免疫组化显示TSN可以减少肝纤维化大鼠肝组织中TGF-β1和肝星状细胞活化标志α-SMA蛋白的表达。结论:TSN具有良好的抗肝纤维化作用,其机制可能与其降低细胞因子TGF-β1的水平进而抑制肝星状细胞(HSC)活化有关。
Objective: To investigate the effect of TanshinoneⅡA (TSN) on hepatic fibrosis in rats and its mechanism. Methods: The animal model of hepatic fibrosis was induced by carbon tetrachloride (CCl 4). The Wistar rats were randomly divided into normal group, CCl 4 model group, positive control Bifendate group (100mg / kg), T5N high, medium and low doses (21.3,14.2,7.1mg / kg) Gavage for 6 weeks. At the end of the treatment, animals were killed by blood sampling and the serum was separated to observe the effect of TSN on the biochemical indexes of chronic hepatic fibrosis rats. The fixed part of the liver tissues were taken for the determination of hydroxyproline content and histopathological examination. The liver tissues were observed by immunohistochemistry The expression of transforming growth factor (TGF-β1) and α-smooth muscle actin (α-SMA). Results: TSN could reduce the levels of HA, LN and Hyp (P <0.05, P <0.01) in serum of rats with hepatic fibrosis; HE and Masson TSN could improve the pathological damage of hepatic fibrosis by special staining of collagen fibers. Immunohistochemistry of liver tissue showed that TSN could reduce the expression of TGF-β1 and α-SMA of hepatic stellate cells in hepatic fibrosis rats. CONCLUSIONS: TSN has a good anti-hepatic fibrosis effect, which may be related to the decrease of TGF-β1 and the activation of hepatic stellate cells (HSC).