灵芝孢子油对四氯化碳联合高脂饮食诱导大鼠肝纤维化的作用研究

Study on Effects of Ganoderma lucidum Spore Oil on Liver Fibrosis in Rats Induced by Carbon Tetrachloride Combined with High-Fat Diet

探究灵芝孢子油(GSO)对四氯化碳(CCl_(4))联合高脂饮食诱导的大鼠肝纤维化的改善作用及机制。将雄性SPF级SD大鼠分为空白对照组、模型对照组、阳性药物组和灵芝孢子油低、中、高剂量组(人体推荐量的5、15、30倍)。采用CCl_(4)联合高脂饲料诱导6周建立大鼠肝纤维化模型,造模过程中灌胃GSO干预8周。通过检测血清生理生化指标和大鼠肝脏组织形态、氧化应激水平、纤维化相关蛋白,评价GSO对肝纤维化的保护作用。研究结果表明,中、高剂量GSO能够显著提升肝纤维化大鼠的存活率,使得大鼠存活率恢复至空白对照组水平。病理染色结果表明,GSO处理的大鼠肝组织纤维化得到不同程度的改善,GSO中、高剂量处理显著降低大鼠肝脏胶原面积占比及面密度。GSO高剂量干预可显著降低大鼠血浆肝功能相关指标(谷丙转氨酶、谷草转氨酶、总胆红素、碱性磷酸酶)水平,减少血浆中肝纤维化指标(透明质酸、层黏蛋白、Ⅳ型胶原、羟脯氨酸)水平。同时,高剂量GSO干预还显著降低肝组织中丙二醛含量,提高还原型谷胱甘肽含量与超氧化物歧化酶活性,显著升高基质金属蛋白酶-9的表达。研究结果证实,中、高剂量GSO(人体推荐量的15、30倍)可提高肝纤维化模型大鼠存活率、抗氧化能力,具有改善大鼠生存状态和肝脏纤维化的作用。

The effects of Ganoderma lucidum spore oil(GSO)on liver fibrosis in rats induced by carbon tetrachloride(CCl_(4))combined with high-fat diet was investigated,and its potential mechanism was explored.Male SPF SD rats were divided into blank control group,model control group,positive drug group,and GSO low,medium and high dose groups.The liver fibrosis model was induced by CCl_(4) combined with high-fat diet for 6 weeks,and GSO was administered for 8 weeks at the same time.The protective effect of GSO on liver fibrosis was evaluated by detecting the serum physiological and biochemical indexes,morphology of rat liver slices,oxidative stress,and fibrosis related proteins of rat liver tissue.The results showed that GSO could significantly improve the survival rate of rats with liver fibrosis,making the survival rate recover to the level of the blank control group.The results of pathological staining showed that the liver tissue structure was improved in different degrees in each group,and the proportion of collagen area and areal density in the GSO middle and high dose groups was significantly decreased.The high dose group could significantly reduce the levels of plasma liver function-related indexes,the contents of liver fibrosis indexes.Meconwhile,GSO high dose group significantly decreased the content of MDA,increase the content of GSH,the activity of SOD survival status,liver fibrosis,and the expression of MMP-9.The results showed that middle and high dose of GSO(15 and 30 fold recommended dosage of human body)could improve the survival rate and antioxidant capacity of liver fibrosis model rats and had the protective effect on rat survival rate and liver fibrosis.