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扶正化瘀胶囊对肝纤维化大鼠的防治作用及对结缔组织生长因子表达的影响

Prevention and Therapeutic Effects of Fuzheng Huayu Capsule on Liver Fibrosis and Expression of Connective Tissue Growth Factor in Rats

  • 摘要: 目的 研究扶正化瘀胶囊在实验性肝纤维化形成中的预防作用及肝纤维化形成后的治疗作用,分析扶正化瘀胶囊对肝纤维化大鼠结缔组织生长因子(CTGF)表达的影响,探讨其可能的作用机制。方法 选取Wistar大鼠40只随机分为正常组(8只)、预防组(预防实验组8只和预防对照组8只)和治疗组(治疗实验组8只和治疗对照组8只);除正常组外,其余各组均采用皮下注射CCl4联合饮用乙醇的方法制备肝纤维模型;预防实验组和治疗实验组分别在造模第4周和造模结束后(第8周)予扶正化瘀方生药0.46 g/kg体质量灌胃。每日1次,共4周;预防对照组和治疗对照组分别于上述时点予生理盐水10 mL/kg体质量灌胃,实验结束后分别采血测定肝功能、肝纤维化指标,对肝组织进行病理学观察,并对肝组织内的CTGF蛋白进行免疫组织化学染色分析。结果 造模结束后(第8周),预防实验组较预防对照组的总胆红素(TB)、谷丙转氨酶(ALT)降低,差异有统计学意义( P均<0.05)。第12周,治疗实验组较治疗对照组的ALT降低,差异有统计学意义( P<0.01),而其余项差异均没有统计学意义。预防实验组较预防对照组的肝纤维化指标透明质酸(HA)降低,差异有统计学意义( P<0.01)。治疗实验组较治疗对照组的肝纤维化指标层粘连蛋白(LN)降低,差异有统计学意义(P<0.05),其余项差异没有统计学意义。治疗实验组较治疗对照组的肝组织病理显示其炎症及肝纤维化均明显减轻,治疗实验组肝组织CTGF表达低于治疗对照组,差异有统计学意义(P<0.05)。结论 扶正化瘀胶囊在实验性肝纤维化造模过程中有预防肝纤维化形成的作用,在实验性肝纤维化形成后具有逆转肝纤维化的治疗作用。肝纤维化大鼠肝组织中CTGF表达明显增加,而扶正化瘀胶囊可抑制CTGF表达,可能是其作用机制之一。

     

    Abstract: Objective To investigate the prevention and therapeutic effects of Fuzheng Huayu Capsule on liver fibrosis in rats and its possible mechanism by regulating the expression of connective tissue growth factor (CTGF).Methods Forty Wistar rats were randomly divided into five groups: the normal group, the preventive group (the preventive experimental group and the preventive control group) and the treatment group (the treatment experimental group and the treatment control group). All the rats, except those in the normal group, were given CCl4 by subcutaneous injection and alcohol by oral adminstration to establish the model of liver fibrosis; meanwhile the rats in normal group were given same amount of olive oil by subcutaneous injection and water by oral administration. The preventive experimental group and control group were treated with Fuzheng Huayu crude drug 0.46 g/kg body mass through stomach irrigation and saline respectively once a day for four weeks during the modeling process. The treatment experimental group and control group were treated with Fuzheng Huayu crude drug 0.46 g/kg body mass through stomach irrigation and saline respectively once a day for four weeks after the modeling process. Blood was collected for the examination of liver function and serum fibrosis marker. HE staining was used to examine the pathological changes in liver tissue. The expression of CTGF was detected by immunohistochemistry. Results Compared with the preventive experimentalgroup, total bilirubin(TB), alanine aminotransferase(ALT)and hyaluronic acid(HA)in the preventive control group decreased significantly ( P<0.05). Compared with the treatment control group, ALT and laminin(LN in the treatment experimental group decreased significantly ( P<0.01). Compared with the treatment comtrol group, the inflammation and hepatic fibrosis in the treatment experimental group alleviated significantly. The expression of CTGF in the treatment experimental group were significantly lower than that in the treatment control group ( P<0.05). Conclusion Fuzheng Huayu Capsule showed the prevention and therapeutic effects on experimental liver fibrosis. Meanwhile, Fuzheng Huayu Capsule could inhibit the CTGF expression in liver tissue, which may be one of the molecular mechanisms of these effects.

     

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