三甲益肝颗粒对肝纤维化大鼠Ⅰ型和Ⅲ型前胶原mRNA表达的抑制作用

Inhibition of Sanjiayigan granule on expressions of procollagen typeⅠand Ⅲ mRNA in hepatic fibrosis rats

目的研究三甲益肝颗粒(SJG)对四氯化碳(CCl4)诱导的大鼠肝纤维化(HF)的抑制作用,并探讨其可能的作用机制。方法健康SD大鼠50只分为3组:模型组(n=18)和SJG组(n=17)采用体积分数40%CCl4花生油溶液皮下注射,每周2次,诱导HF模型;同时,SJG组给予SJG灌胃,模型组给予蒸馏水灌胃,每天均1次;对照组(n=15)采用皮下注射生理盐水,每周2次,并给予蒸馏水灌胃,每天1次。分别于第6周末、第8周末取肝组织观察病理组织学变化;逆转录-聚合酶链反应(RT-PCR)检测Ⅰ、Ⅲ型前胶原(Ⅰ-PC、Ⅲ-PC)mRNA的表达。结果与同期模型组相比,SJG组坏死、炎症反应及纤维化程度显著减轻(P<0.01);第6周末时胶原纤维集中在中央静脉和汇管区周围,少数汇管区纤维化扩大,形成细小、菲薄的纤维间隔,但小叶结构保留;第8周末时可见较宽的纤维间隔,但未形成假小叶。模型组Ⅰ-PC、Ⅲ-PC mRNA的表达较正常对照组显著增加(P<0.01),SJG组与模型组相比显著减少(P<0.01)。结论SJG能减轻中毒大鼠肝脏坏死及炎症,抑制Ⅰ-PC、Ⅲ-PC mRNA的表达,从而抑制HF。

Objective To investigate the inhibitive effect of Sanjiayigan granule （SJG） on carbon tetrachloride （CCl4 ）- induced hepatic fibrosis in rats, and approach the mechanism of prevent experimental hepatic fibrosis by SJG. Methods Fifty male SD rats were randomly divided into three groups. The rats in model group（n = 18） and SJG group（n = 17） ,40% CCl4 solution diluted by peanut oil were given by subcutaneous injection two times a week to establish hepatic fibrosis model, meanwhile, SJG and distilled water were given by intragastric administration to the rats in the SJG group and the model once a day respectively. The rats in control group（ n = 15 ）, normal saline were only given subcutaneously, two times a week, and distilled water were given by intragastric administration once a day. Hepatic tissue were collected at end of 6^th and 8^th week respectively. The histological changes of liver were examined. The expressions of procollagen type Ⅰ and type Ⅲ mRNA were measured by reverse transcriptase-polymerase chain reaction （RT-PCR）. Results In SJG group, the degeneration, necrosis,inflammation and fibrosis in hepatic tissue decreased obviously compared with the model group in the corresponding time period（ P 〈 0.01 ）. In the SJG group at the 6th week, hepatic fibrosis in portal areas, central veins and some thin fibrous intervals were observated. However, the structure of liver lobules was still maintained. In the SJG group at the 8th week, there were some thick fibrous septas in some slices,but not pseudolobules. The expressions of procollagen type Ⅰ and Ⅲ mRNA in the model group increased obviously compared with the normal group （ P 〈 0.01 ）, it decreased obviously in the SJG group compared with the model group （ P 〈 0. 01 ）. Conclusion The SJG can lighten necrosis and inflammatory reaction in liver, and inhibit the expressions of procollagen type Ⅰ and Ⅲ mRNA in rats. So it can decrease the degree of experimental hepatic fibrosis.