肝纤维化大鼠模型STAT3mRNA的动态变化及贝那普利对其的影响

Dynamic expression of STAT3 mRNA in CCL_4-induced rat liver fibrosis model and the effect of Benazepril on these changes

目的探讨大鼠肝纤维化形成过程中信号转导转录因子3(signal transduction of transcription factor,STAT3)mRNA表达的动态变化以及贝那普利可能的抗纤维化机制,为肝纤维化的临床防治提供实验依据。方法用随机数字表法将40只SD大鼠随机分为3组,正常对照组(n=6)、模型组(n=26)、治疗组(n=8),各组肝损伤和肝纤维化的评估采用肝组织HE染色和Masson染色,逆转录-聚合酶链反应(reverse transcription polymerase chain reaction,RT-PCR)检测肝组织中STAT3mRNA表达变化。结果随着肝组织炎症及纤维化的逐渐加重,STAT3mRNA表达6周(221.459±51.362)达高峰、8周(120.939±24.764)开始下降,较正常组(51.160±16.427)明显升高(P<0.05)。而给予贝那普利干预后,肝组织STAT3mRNA表达(75.031±9.203)较模型组(120.939±24.764)明显减少(P<0.05)。结论 STAT3可能是肝损伤、慢性肝炎致肝纤维化形成过程中不可或缺的关键性分子,而贝那普利则可能通过抑制STAT3mRNA的表达从而抑制肝星状细胞的活化发挥其抗纤维化作用。

Objective To investigate the dynamic changes of signal transducer and activator of transcription 3 （ STAT3 ） mRNA expression in the process of liver fibrosis formation and study the molecular action mechanism of Benazepril in treating the liver fibrosis model, and to provide an experimental evidence for the new drug treating of liver fibrosis. Methods SD rats were randomly divided into three groups using random number table method ： control group （ n = 6 ）, model group （ n = 26 ） and Benazepril intervention group （n = 8 ）. Both hematoxy!in-eosin （HE）staining and Masson staining were performed to evaluate the degree of liver damage and liver fibrosis. The expression change of STAT3 mRNA was determined by reverse transcription polymerase chain reaction （RT-PCR）. Results STAT3 mRNA expression was gradually increased in the process of liver inflammation and fibrosis, and it reached the peak at 6 weeks （221. 459± 51. 362） ,while declined at the 8 weeks （ 120. 939 ± 24. 764）, obviously higher than that in control group （51. 160 ± 16. 427, P 〈 0. 05 ）. When intervened with Benazepril, STAT3 mRNA expression was significantly decreased compared with model group （75. 031 ± 9. 203 vs. 120. 939 ± 24. 764 ,P 〈 0. 05 ）. Cortelusions STAT3 is possibly an indispensable key member in the process of liver fibrosis induced by liver damage and chronic hepatitis. Benazepril may further inhibit hepatic stellate cell activation via inhibiting STAT3 mRNA and therefore plays an efficient role against liver fibrosis.