参芪扶正注射液对酒精性肝纤维化大鼠ROS、SOD、LPO、NF-κB及CTGF mRNA表达的干预作用

Effect of Shenqi Fuzheng Injection on serum levels of ROS, SOD, LPO, NF-κB and CTGF mRNA expression in rats with alcoholic hepatic fibrosis

目的:研究ROS、SOD、LPO、NF-B及CTGF mRNA在酒精性肝纤维化大鼠中的表达状况及参芪扶正注射液的干预作用.方法:SD大鼠100只,随机分为正常对照组、模型组和参芪扶正注射液小剂量治疗组2.0mL/(100g·d)、中剂量治疗组2.5mL/(100g·d)、大剂量治疗组3.0mL/(100g·d).以乙醇灌胃诱导大鼠肝纤维化模型,治疗组造模同时给予参芪扶正注射液尾静脉注射,共16wk.16wk后处死大鼠取肝组织标本,光镜观察肝组织的病理变化,放射免疫法测定血清ROS、SOD、LPO含量及NF-B活性,逆转录-聚合酶链反应(RT-PCR)法检测肝组织结缔组织生长因子(CTGF)mRNA表达.结果:与正常组比较,模型组SOD显著下降,肝组织纤维化积分、ROS、LPO、NF-B活性及CTGF mRNA表达显著增加(P<0.01);与模型组比较,治疗组SOD显著上升,肝组织纤维化积分、ROS、LPO、NF-B活性及CTGF mRNA表达显著下降(P<0.01),肝组织纤维化积分和ROS、LPO及CTGF mRNA表达呈正相关关系(r=0.463、0.425、0.412,均P<0.05).结论:脂质过氧化、NF-B活化、CTGF与酒精性肝纤维化的严重程度密切相关,3者对酒精性肝纤维化发生、发展有协同作用,参芪扶正注射液能显著抑制脂质过氧化、降低NF-B活性及CTGF mRNA表达,从而减轻肝组织损害严重程度.

AIM： To explore the effect of Shenqi Fuzheng Injection on serum levels of ROS, SOD, LPO, NF-B and CTGF mRNA expression in rats with alcoholic hepatic fibrosis. METHODS： One hundred male SD rats were divided into normal group, model group, low [（2.0 mL/（100 g d）], medium [（2.5 mL/（100 g d）] and high-dose [（3.0 mL/（100 g d）] Shenqi Fuzheng Injection groups. Rats were intragastrically administered with alcohol for 16 wk to induce hepatic fibrosis. Shenqi Fuzheng Injection was injected into the tail vein of rats in the three treatment groups. The rats were killed after 16 wk. The histological structure of the liver tissue was observed under an optical microscope, the levels of ROS, SOD, LPO and NF-B in serum were determined by radioimmunoassay, and the expression of connective tissue growth factor （CTGF） mRNA was measured by reverse transcriptase-polymerase chain reaction （RT-PCR）. RESULTS： Compared to the normal group, the level of serum SOD decreased significantly and the fibrosis score and the levels of ROS, LPO, NF-B and CTGF mRNA increased significantly in the model group （all P 〈 0.01）. Compared to the model group, the level of serum SOD increased significantly and the fibrosis score and the levels of ROS, LPO, NF-B and CTGF mRNA decreased significantly in the treatment groups （all P 〈 0.01）. The levels of ROS, LPO and CTGF mRNA were positively correlated with the fibrosis score （r = 0.463, 0.425, 0.412, all P 〈 0.05）. CONCLUSION： Lipid peroxidation, NF-B activation and CTGF are closely related to the severity of alcoholic hepatic fibrosis, and there may be a synergetic interaction among lipid peroxidation, NF-B and CTGF in the pathogenesis of alcoholic hepatic fibrosis. Shenqi Fuzheng Injection can inhibit lipid peroxidation, decrease NF-B activity and CTGF mRNA expression and thereby alleviate the severity of hepatic fibrosis in rats with alcoholic hepatic fibrosis.