假木豆对CCl_(4)致大鼠肝损伤的保护作用

Protective Effect of Jiamudou(Dendrolobium Triangulare)on CCl_(4) Induced Liver Injury in Rats

目的:探讨假木豆对CCl4致大鼠肝损伤的保护作用和机制。方法:30只大鼠随机分为模型组、联苯双酯组和假木豆组,每组10只,采用CCl4制备肝损伤大鼠模型,另选取10只大鼠作为空白对照组。空白对照组和模型组大鼠予生理盐水灌胃,10 mL/kg;联苯双酯组大鼠予复方联苯双酯片溶液灌胃,100 mg/kg;假木豆组大鼠予假木豆水提物灌胃,100 mg/kg;1次/周,连续6周。末次给药后禁水12 h、禁食24 h,称量大鼠体质量,经腹主动脉取血分离血清,颈椎脱臼法处死,取肝组织称质量计算肝脏指数,HE染色观察肝组织病理变化,检测血清肝功能指标(TBIL、ALT、AST)变化,ELSIA法检测炎症因子水平(TNF-α、IL-1、IL-6、IL-10)变化,肝组织匀浆检测氧化损伤指标(MDA、SOD、GSH)变化,RT-PCR检测肝纤维化因子基因(HA mRNA、α-SMA mRNA、TGF-β1 mRNA)水平变化。结果:模型组大鼠肝细胞排列紊乱,可见广泛的肝细胞脂肪变性及水肿、纤维组织增生等,胞质界限模糊,伴有炎症细胞浸润。与空白对照组比较,模型组大鼠血清TBIL、ALT、AST、MDA、IL-1、IL-6、TNF-α水平,肝脏指数均明显升高,血清SOD、GSH、IL-10水平明显降低(P<0.05);与模型组比较,联苯双酯组和假木豆组大鼠血清TBIL、ALT、AST、MDA、IL-1、IL-6、TNF-α水平,肝脏指数均明显降低,血清SOD、GSH、IL-10水平明显升高(P<0.05);假木豆组大鼠血清TBIL、ALT、AST、MDA、SOD、GSH、IL-1、IL-6、TNF-α、IL-10水平,肝脏指数与联苯双酯组比较,差异均无统计学意义(P>0.05)。与空白对照组比较,模型组大鼠HA mRNA、α-SMA mRNA、TGF-β1 mRNA相对表达量明显升高(P<0.05);与模型组比较,联苯双酯组和假木豆组大鼠HA mRNA、α-SMA mRNA、TGF-β1mRNA相对表达量明显降低(P<0.05);假木豆组大鼠HA mRNA、α-SMA mRNA、TGF-β1 mRNA相对表达量与联苯双酯组比较,差异均无统计学意义(P>0.05)。结论:假木豆能够有效改善CCl4致大鼠肝损伤,对肝功能具有良好的保护作用,其作用机制可能与抗氧化应激、抑制炎症反应、阻断肝纤维化有关。

Objective:To investigate the protective effect and mechanism of Jiamudou(Dendrolobium Triangulare)on liver injury induced by CCl4 in rats.Methods:A total of 30 rats were randomly divided into model group,bifendate group and Jiamudou group,with 10 rats in each group.CCl4 was used to prepare rat models of liver injury,and another 10 rats were selected as blank control group.Rats in the blank control group and model group were given normal saline(10 mL/kg)by gavage,rats in the bifendate group were given compound bifendate tablets solution(100 mg/kg)by gavage,and rats in Jiamudou group were given the water extract of Jiamudou(Dendrolobium Triangulare)(100 mg/kg)by gavage,once a week for 6 consecutive weeks.After the last administration,the rats were deprived of water for 12 hours and fasted for 24 hours.The weight of the rats was measured.The blood was taken from the abdominal aorta to separate the serum.The rats were killed by cervical dislocation.The liver tissue was weighed and the liver index was calculated.HE staining was used to observe the pathological changes of liver tissue.The changes of serum liver function indexes(TBIL,ALT,AST)were detected.The levels of inflammatory factors(TNF-α,IL-1,IL-6,IL-10)and MDA,SOD,GSH in liver homogenate were detected by ELSIA method.The levels of hepatic fibrosis factors(HA,α-SMA,TGF-β1)were detected by RT-PCR.Results:The arrangement of hepatocytes was disordered in rats with liver injury.Extensive fatty degeneration and edema of hepatocytes,fibrous tissue hyperplasia were observed.The boundary of the cytoplasm was blurred,accompanied by inflammatory cell infiltration.Compared with the blank control group,the serum levels of TBIL,ALT,AST,liver index,MDA,IL-1,IL-6 and TNF-αin the model group were significantly increased,while the serum levels of SOD,GSH and IL-10 were significantly decreased(P<0.05).Compared with the model group,the serum levels of TBIL,ALT,AST,MDA,IL-1,IL-6 and TNF-αin the bifendate group and the Jiamudou group were significantly reduced,and the liver index was significantly reduced,and the serum levels of SOD,GSH,IL-10 were significantly increased(P<0.05).There was no significant difference in the serum levels of TBIL,ALT,AST,MDA,SOD,GSH,IL-1,IL-6,TNF-α,IL-10 and liver index between the bifendate group and the Jiamudou group(P>0.05).Compared with the model group,the relative expressions of HA mRNA,α-SMA mRNA,and TGF-β1 mRNA in the bifendate group and the Jiamudou group were significantly reduced(P<0.05).There was no significant difference in the relative expression of HA mRNA,α-SMA mRNA and TGF-β1 mRNA between the bifendate group and the Jiamudou group(P>0.05).Conclusion:Jiamudou(Dendrolobium Triangulare)can effectively improve the liver injury caused by CCl4 in rats,and has a good protective effect on liver function.Its mechanism may be related to anti-oxidative stress,inhibiting inflammation,and blocking liver fibrosis.