目的:四氯化碳(CCL4)毒性引发纤维化,激活细胞内的各种机制。我们旨在用CCL4产生损伤,并研究L-肉碱对我们确定的机制的有效性。
方法:将40只大鼠分为5组,每组数量相等。第一组:对照组,第二组:左旋肉碱组,200毫克/千克左旋肉碱每周两次,第三组:CCL4组,0.2毫升/100克CCL4,IP,在6周内每周2次溶解于橄榄油;IV组:左旋肉碱+CCL4组,200毫克/千克L-肉碱24小时前0.2毫升/100克CCL4应用每周两次;组V:CCL4+L-肉碱,200mg/kgL-肉碱半小时后0.2ml/100gCCL4施用。对肝脏进行组织学评价。免疫组织化学α-SMA染色,iNOS,HSP90,HIF-1α,和RIP1。TNF-α,TGF-β,AST,ALT,ALP,和GGT测量进行了评估。
结果:在经典的小叶外围,观察到脂质积累的增加和糖原积累的减少。经过免疫组织化学测量和生化分析,在第III组中观察到所有蛋白质的表达密度增加。在IV组和V组中,观察到组织改善和蛋白质表达密度降低.
结论:iNOS可作为自由基清除剂,以应对由α-SMA毒性增加引起的损伤,HSP90和HIF-1α。尤其是,组织中增加的RIP1水平表明在CCL4毒性后组织中存在坏死。用补充剂补充内源性L-肉碱的量提供了组织的显著改善。
OBJECTIVE: Carbon tetrachloride (CCL4) toxicity triggers fibrosis, activating various mechanisms within the cell. We aimed to create damage with CCL4 and investigate the effectiveness of L-carnitine on the mechanisms we identified.
METHODS: Forty rats were divided into 5 groups with equal number of rats in each group. Group I: Control group, Group II: L-carnitine group, 200 mg/kg L-carnitine twice a week, Group III: CCL4 group, 0.2 ml/100 gr CCL4, IP, dissolved in olive oil 2 times a week during 6 weeks; Group IV: L-carnitine + CCL4 group, 200 mg/kg L-carnitine 24 hr before 0.2 ml/100 g CCL4 application twice a week; Group V: CCL4 + L-carnitine, 200 mg/kg L-carnitine half an hour after 0.2 ml/100 g CCL4 application. The liver was evaluated histologically. Immunohistochemically stained with α-SMA, iNOS, HSP90, HIF-1α, and RIP1. TNF-α, TGF-β, AST, ALT, ALP, and GGT measurements were evaluated.
RESULTS: In the classical lobule periphery, an increase in lipid accumulation and a decrease in glycogen accumulation were observed. After immunohistochemical measurements and biochemical analyzes, an increase in the expression density of all proteins was observed in group III. In group IV and V, an improvement in tissue and a decrease in protein expression densities were observed.
CONCLUSIONS: iNOS serves as a free radical scavenger in response to damage caused by increased toxicity of α-SMA, HSP90, and HIF-1α. Especially, increased RIP1 level in the tissue indicates the presence of necrosis in the tissue after CCL4-toxicity. Supplementing the amount of endogenous L-carnitine with supplementation provides a significant improvement in the tissue.