虫草菌丝提取物干预与治疗二甲基亚硝胺诱导大鼠肝硬化的实验研究

作者	单位
王宪波	上海中医药大学附属曙光医院肝病研究所
刘平	上海中医药大学附属曙光医院肝病研究所
唐志鹏	上海中医药大学附属曙光医院肝病研究所
李风华	上海中医药大学附属曙光医院肝病研究所
刘成海	上海中医药大学附属曙光医院肝病研究所
胡义杨	上海中医药大学附属曙光医院肝病研究所
徐列明	上海中医药大学附属曙光医院肝病研究所

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中文摘要:

目的明确虫草菌丝提取物(Cordyceps mycelia extract,CME)对二甲基亚硝胺(dimethylnitro-samine,DMN)诱导大鼠肝硬化的干预与治疗作用。方法采用DMN10μg/kg剂量腹腔内注射,每日1次,每周前3日、持续4周的方法制备大鼠肝硬化模型。CME干预实验于造模即日起开始灌胃给药至造模4周末;治疗实验于造模4周、终止造模因素后开始给药至8周末;均以0.74g/(kg.d)剂量给予CME,每日1次。分别于造模后3天、2、4、6、8周处死动物取材进行动态效应观察。观测肝组织学、肝组织α平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原(ColⅠ)的免疫组织化学染色、肝羟脯氨酸(Hyp)含量以及肝功能的检测。结果与同期模型组比较,CME预防给药后2、4周的血清丙氨酸氨基转移酶(ALT)、血清门冬氨酸氨基转移酶(AST)活性和血清总胆红素(TBIL)含量均显著降低(P<0.05),血清白蛋白(Alb)含量显著增加(P<0.05);干预用药4周后的肝Hyp含量显著下降(P<0.05),胶原纤维增生程度显著减轻(P<0.05),肝组织内α-SMA、ColⅠ阳性表达显著减少(P<0.05)。与同期模型组比较,治疗给药2周后的血清ALT、AST活性和血清TBIL含量显著降低(P<0.05),血清Alb含量有所升高(P>0.05);治疗给药2、4周的肝Hyp含量均显著降低(P<0.05),胶原纤维增生程度均显著减轻(P<0.05),肝组织α-SMA表达均显著减少(P<0.05);治疗给药4周时肝组织ColⅠ表达显著减少(P<0.05)。结论CME既能显著抑制DMN大鼠肝硬化的形成,也可有效促进已成型的DMN大鼠肝硬化的逆转,具有良好的临床应用前景。

英文摘要:

Objective To explore the intervening and therapeutic effect of Cordyceps mycelia extract(CME) on liver cirrhosis induced by dimethylnitrosamine(DMN) in rats.Methods Rat liver cirrhosis model was established by peritoneal injection of DMN at a dose of 10 μg/kg,once daily in the first 3 days of every week for 4 successive weeks.Experimental study on CME-intervention was conducted from the beginning of modeling to the end of the 4th week,while the CME-treatment experiment was carried out from the 4th week of modeling,when terminating the modeling factor,to the end of the 8th week,by administering CME at a dose of 0.74 g/(kg·d) once a day.Animals were killed in batches on the 3rd day,the 2nd(T1),4th(T2),6th(T3) and 8th(T4) week after modeling,to observe the histopathologic change in liver and the immunohistochemical staining of alpha-smooth muscle actin(α-SMA) and collagen type Ⅰ(Col Ⅰ),determine the content of hydroxyproline(Hyp) in liver,and the liver function was tested as well.Results CME-intervention experiment showed that as compared to those in the modeled rats at corresponding time points,in rats at T1 and T2,serum alanine aminotransferase(ALT),aspartate aminotransferase(AST) activity and total bilirubin(TBIL) content were significantly lower,and albumin(Alb) obviously higher;while at T2,Hyp content,α-SMA and ColⅠ positive expression were significantly lower(P<0.05),the proliferation of collagen fibre attenuated.CME-treatment experiment showed that as compared to those in the modeled rats at corresponding time points,lower serum ALT,AST activity and TBIL content,and higher serum level of Alb were shown in rats at T1;and lower Hyp content,liver collagen fibre,and α-SMA positive expression were shown at T1 and T2;while less ColⅠ positive expression at T2 was also shown in them(all P<0.05).Conclusion CME could not only prevent the development of liver cirrhosis induced by DMN in rats,but also effectively promote the reversion of already formed liver cirrhosis,having a favourable prospect of clinical application.

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