茵虎清肝方对D-氨基半乳糖脂多糖诱导的急性肝衰竭模型大鼠肝损伤的影响

目的观察茵虎清肝方对D-氨基半乳糖脂多糖诱导的急性肝衰竭模型大鼠肝损伤的影响并探讨其作用机制。方法 60只大鼠随机分为空白组、模型组、阳性组、实验组。采用腹腔注射D-氨基半乳糖脂多糖建立急性肝衰竭大鼠模型。阳性对照组给予安宫牛黄丸灌胃、实验组给予茵虎清肝方药液灌胃。检测血清谷丙转氨酶(ALT)、谷草转氨酶(GOT)以及总胆红素(TBIL)水平,观察肝脏组织病理学变化,采用ELISA检测检测肝脏组织中炎症因子肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、I白细胞介素-6(L-6)表达以及超氧化物歧化酶(SOD)、谷胱甘肽(GSH)和丙二醛(MDA)水平的变化,检测肝脏纤维化指标透明质酸酶(HA)、层黏连蛋白(LN)、Ⅲ型前胶原(Ⅲ-PC)和Ⅳ型胶原及肝细胞凋亡情况。结果模型组肝细胞排列紊乱、细胞水肿变性坏死,肝索紊乱,炎性细胞浸润,纤维组织增生,肝窦区扩张并充血。给予药物干预后,阳性组和实验组大鼠的肝细胞形态结构稍紊乱,肝细胞肿胀减轻,坏死肝细胞减少,结节状也少,纤维组织减少。模型组大鼠的ALT、GOT、TBIL、肝脏指数以及肝纤维化指标明显升高(P <0.05)。给予药物干预后,阳性组和实验组的ALT、GOT、TBIL、肝脏指数、HA、LN、Ⅲ-PC以及Ⅳ-C水平明显低于模型组,两组间差异有统计学意义(P <0.05)。模型组大鼠的SOD和GSH含量明显降低,TNF-α、IL-1β、IL-6水平和MDA含量明显升高;药物干预后,阳性组和实验组大鼠SOD和GSH含量明显升高(P <0.05),TNF-α、IL-1β、IL-6水平和MDA含量明显降低(P <0.05)。阳性组和实验组大鼠的SOD、GSH和MDA含量、TNF-α、IL-1β以及IL-6水平差异有统计学意义(P <0.05)。结论茵虎清肝方通过抑制炎症反应、减少氧化应激,阻断肝脏纤维化对D-氨基半乳糖脂多糖诱导的大鼠急性肝衰竭发挥保护作用。

Effect of Yinhu Qinggan Granules on Liver Injury Induced by D-galactosamine Lipopolysaccharide in Rats with Acute Hepatic Failure

Objective:To investigate the effect and mechanism of Yinhu Qinggan Granules on liver injury induced by D-galactosamine lipopolysaccharide in rats with acute liver failure. Methods:60 rats were randomly divided into the blank group,the model group,positive group and the experimental group. Rat models of acute liver failure was established by intraperitoneal injection of D-galactosamine lipopolysaccharide. The positive group was given Angong Niuhuang Pills,and the experimental group was given Yinhu Qinggan Granules. The levels of serum ALT,AST and TBIL were measured,and the pathological changes of liver tissues were observed. The expressions of inflammatory factors TNF-α,IL-1β,IL-6 and the levels of SOD,GSH and MDA in liver tissues were detected by ELISA. The indicators of HA,LN,III-PC and type IV collagen and hepatocyte apoptosis were detected. Results:The model group had disordered hepatocyte arrangement,cell edema degeneration and necrosis,hepatic cord disorder,inflammatory cell infiltration,fibrous tissue hyperplasia,dilated hepatic sinus and hyperemia. After drug intervention,the liver cells in the positive group and the experimental group were slightly disordered in hepatocyte morphology;the hepatocyte swelling was reduced;the necrotic hepatocytes were reduced;the nodular shape was less,and the fibrous tissue was reduced. ALT,AST,TBL,liver index and liver fibrosis indexes of the model group were significantly increased(P < 0.05). After drug intervention,the levels of ALT,AST,TBL,liver index,HA,LN,III-PC and IV-C in the positive and experimental groups were significantly lower than those in the model group,and there was significant difference between the two groups(P < 0.05). The levels of SOD and GSH were significantly decreased,and the levels of TNF-α,IL-1β,IL-6 and MDA were significantly increased in the model group. After drug intervention,the contents of SOD and GSH were significantly increased(P < 0.05),and TNF-α,IL-1β,IL-6 levels and MDA content were significantly decreased in the positive and experimental groups(P <0.05);those were significantly different between them(P < 0.05). Conclusion:Yinhu Qinggan Granules plays a protective role in acute liver failure induced by D-galactosamine polysaccharide by inhibiting inflammatory reaction,reducing oxidative stress and blocking liver fibrosis.