解毒护肝汤对药物性肝损伤大鼠MMP-2蛋白表达的影响

目的通过检测大鼠血清肝功能指标、血清生物标志物、MMP-2蛋白表达,观察解毒护肝汤对药物性肝损伤大鼠的干预作用及作用机制。方法将大鼠按体质量随机分为正常组、模型组、水飞蓟宾阳性对照组、解毒护肝汤高、中、低剂量组。其中模型组和各给药组给予对乙酰氨基酚药液灌胃复制肝损伤模型,正常组和模型组给予生理盐水灌胃,其余各组给予相应药液灌胃,连续给药30 d。实验结束时,检测谷草转氨酶(AST)、谷丙转氨酶(ALT)、总胆红素(TBIL)、直接胆红素(DBIL)、苹果酸脱氢酶(MDH)、对氧磷酶(PON1)、嘌呤核苷磷酸化酶(PNP)含量变化以及肝组织基质金属蛋白酶2(MMP-2)的蛋白表达情况。结果对乙酰氨基酚大鼠血清AST、ALT、DBIL、PON1、MDH、PNP含量均显著升高(P<0.05,P<0.01),解毒护肝汤中、低剂量组能明显降低转氨酶活性及胆红素含量(P<0.05,P<0.01),高剂量组能显著降低肝损伤大鼠血清PON1、MDH含量(P<0.05),中剂量组明显降低MDH的含量(P<0.05)。肝损伤大鼠MMP-2蛋白阳性表达增多;水飞蓟宾胶囊,对照组以及解毒护肝汤各剂量组阳性表达明显减少。结论解毒护肝汤对APAP所致的药物性肝损伤具有防治作用。

Effect of Jiedu Hugan Decoction on the Expression of MMP-2 Protein in Rats with Drug-induced Liver Injury

Objective To observe the intervention effect and mechanism of Jiedu Hugan decoction on drug-induced liver injury in rats by detecting serum liver function indexes,serum biomarkers and MMP-2 protein expression.Methods The rats were randomly divided into normal group,model group,Silybin control group,high dose,medium dose and low dose of jiedu hugan decoction.The model group and each group were given acetaminophen solution by gavage to replicate the liver injury model,the normal group and the model group was given normal saline solution by gavage,and the other groups were given corresponding solution by gavage for 30 consecutive days.At the end of the experiment,we detected the changes of aspartate aminotransferase(AST),alanine aminotransferase(ALT),total bilirubin(T-BIL),direct bilirubin(D-BIL),malate dehydrogenase(MDH),p-oxyphosphatase(PON1),purine nucleoside phosphorylase(PNP)in serum and the protein expressions of matrix metalloproteinase 2(MMP-2)in liver tissue.Results The serum AST,ALT,DBIL,PON1,MDH,PNP content in rats with given acetaminophen were significantly increased(P<0.05,P<0.01).The low dose group of Jiedu Hugan decoction can obviously decrease transaminase activity and content of bilirubin(P<0.05,P<0.01).The high dose group can significantly reduce serum PON1,MDH levels(P<0.05).The medium dose group can significantly lower MDH levels(P<0.05).Positive expression of MMP-2 protein was increased in rats with liver injury.The positive expression of silybin and jiedu hugan decoction in each dose group decreased obviously.Conclusion Jiedu hugan decoction can prevent and cure the drug-induced liver injury caused by APAP.