双利肝配伍牛磺酸 精氨酸对四氯化碳急性肝损伤的作用及机制的研究

The hepatoprotective effects and underlying mechanism of Shuangligan with/without combined use of arginine and taurine on acute liver injury induced by CCl_4

目的研究双利肝(丹参、大黄合剂)及其配伍牛磺酸、精氨酸对四氯化碳(CCl4)所致急性肝损伤的作用及机制。方法将实验动物随机分为4组:正常对照组、CCl4急性肝损伤组、双利肝治疗组、双利肝+精氨酸+牛磺酸治疗组,除正常对照组外,其余3组分别于实验第1天、第5天给予CCl4皮下注射,后两组分别给予双利肝、双利肝+精氨酸+牛磺酸合剂灌胃。于实验第8天处死动物,取血分别检测各组血浆内毒素(ET)、血清丙氨酸氨基转移酶(ALT)、γ-干扰素(IFN-γ)、白细胞介素-4(IL-4)、IL-2浓度。结果①CCl4急性肝损伤组与正常大鼠组相比,ET、ALT、IL-4水平明显增高(P<0.05或P<0.01),IL-2、IFN-γ水平明显降低(P<0.05)。②与CCl4急性肝损伤组相比,双利肝组ET、ALT、IL-4水平明显下降(P<0.05),IL-2、IFN-γ水平明显增高(P<0.05)。③双利肝+精氨酸+牛磺酸组的ET水平与CCl4急性肝损伤组相比明显降低(P<0.05),但效果不如单独双利肝组,而ALT水平下降却明显优于双利肝组。IL-4水平与双利肝组相比下降明显,IL-2、IFN-γ水平却有明显上升,但IFN-γ水平的变化差异无统计学意义。结论CCl4所致急性肝损伤大鼠存在肠源性内毒素血症(IETM),由此导致免疫功能紊乱,表现为Th1/Th2细胞失衡。经双利肝或双利肝伍用牛磺酸、精氨酸联合治疗,通过降低内毒素水平,调整Th1/Th2比例,从而增强细胞免疫功能,同时减轻肝损伤。由此提示对肝炎治疗若要取得满意疗效应采取综合治疗的对策。

Objective To study the hepatoprotective effects and underlying mechanism of Shuangligan （Misturae Rhei et Salvia Miltiorrhiza） with/without combined use of arginine and taurine on CCI4-induced acute liver injury. Methods Rats were randomized into normal group, acute liver injury group, Shuangligan （SLG） group and SLG＋ arginine＋taurine group （n=6 for each group）. Except for the normal group, the animals were given subcutaneous injection of carbon tetrachloride （CCI4） on days 1 and 5. The SLG and SLG＋arginine＋taurine groups received gavage of SLG and combination of SLG＋arginine＋taurine, respectively. All the rats were sacrificed on day 8. Blood samples were then collected from abdominal aorta for determination of plasma ET, ALT, IL-2, IFN-γ/and IL-4. Results ①Compared with normal group, the acute liver injury group showed increase in ET, ALT and IL-4 levels （P〈0.05 or P〈 0.01 ）, and reduction in IL-2 and IFN-γ/levels （P〈0.05）. ②Compared with the acute liver injury group, levels of ET, ALT and IL-4 in the SLG group were lower （P〈0.05）, while IFN-γ/ and IL-2 were higher （P〈0.05） . ③Compared with the SLG-only group, SLG＋arginine＋taurine group remarkably showed a smaller fall in ET level and a greater reduction in ALT from those in the acute liver injury group （P〈0.05）. Also, there was a lower IL-4 level in the SLG group vs higher levels of IFN-γ/and IL-2 in SLG＋arginine＋taurine group, although the difference in IFN-γ/between these two groups was not statistically significant. Conclusion Rats with acute liver injury group induced by CCI4 may have intestinal endotoxemia, which leads to cellular immune disorder, including Th1/Th2 imbalance. Following SLG or combined therapy with SLG, arginine and taurine, a decrease in the ET level and a modulation in Th1/Th2 ratio may contribute to alleviation of liver injury. Therefor＇e, integrated measures should be justified to reach at a considerable outcome from treatment of hepatitis.