半胱氨酸通过抑制氧化应激和炎症减轻镉诱导的小鼠肝脏脂质代谢紊乱

Cysteine alleviates cadmium-induced disorders of hepatic lipid metabolism inmice by in hibiting oxidative stress and inflammation

为探究半胱氨酸对镉致小鼠肝损伤的保护效应及机制。将SPF小鼠分为对照组、镉组(腹腔注射氯化镉)、镉与低剂量半胱氨酸共处理组(腹腔注射氯化镉+灌胃低剂量半胱氨酸)、镉与高剂量半胱氨酸共处理组(腹腔注射氯化镉+灌胃高剂量半胱氨酸)。给药结束后,测定小鼠血清中谷草转氨酶(aspartate aminotransferase, AST)和谷丙转氨酶(alanine aminotransferase, ALT)活性及肝组织中总胆固醇(total cholesterol, TC)和三酰甘油(triacylglycerol, TG)含量;苏木精-伊红(hematoxylin-eosin, HE)染色观察肝组织病理学变化;微量法检测肝脏组织中丙二醛(malondialdehyde, MDA)含量、超氧化物歧化酶(superoxide dismutase, SOD)和过氧化氢酶(catalase, CAT)活性;ELISA法检测肝脏中IL-6、IL-1β和TNF-α含量;实时荧光定量PCR检测肝脏中脂质代谢相关基因的表达水平。结果表明,与对照组相比,镉暴露小鼠血清ALT与AST活性显著升高(P<0.01),肝组织发生明显肝损伤病理学变化,肝脏中TC和TG含量明显上升(P<0.01),肝脏组织MDA含量显著升高,SOD和CAT活性极显著下降(P<0.01)。半胱氨酸补充可显著改善以上各项指标的异常变化(P<0.05或P<0.01)。此外,补充半胱氨酸可提高镉暴露期间的抗炎潜能,并使促炎细胞因子水平正常化。半胱氨酸还使镉干扰的脂质代谢相关基因的表达正常化,以改善脂质积累,有助于减轻肝损伤。半胱氨酸治疗可降低氧化应激和炎症反应,这可能有助于预防镉诱导的脂质代谢紊乱和肝损伤。

To explore the protective effect and mechanism of cysteine(Cys)on cadmium-induced liver injury in mice.SPF Kunming mice were divided into control group,cadmium(Cd)group(intraperitoneal injection of cadmium chloride),cadmium and low-dose Cys co-treatment group(intraperitoneal injection of cadmium chloride plus oral administration of low-dose Cys),cadmium and high-dose Cys co-treatment group(intraperitoneal injection of cadmium chloride plus oral administration of high-dose Cys).After the treatment,the activities of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)in serum and the contents of total cholesterol(TC)and triacylglycerol(TG)in liver tissue were determined;The pathological changes of liver tissue were observed via HE staining.The content of malondialdehyde(MDA),the activities of superoxide dismutase(SOD)and catalase(CAT)in liver tissue were detected by microvolume assay;The levels of IL-6,IL-1βand TNF-αin liver were detected by ELISA.The expression levels of genes related to lipid metabolism in liver were measured by qRT-PCR.The results showed that the activities of serum ALT and AST were significantly increased in Cd-exposed mice compared to the control group(P<0.01).The liver tissue had obvious pathological changes and the contents of TC and TG in the liver were significantly increased(P<0.01).The level of MDA in liver tissue was significantly increased,and the activities of SOD and CAT were significantly decreased(P<0.01).The supplementation of Cys can significantly improve the adverse changes of the indicators above(P<0.05 or P<0.01).In addition,Cys supplementation enhanced anti-inflammatory potential during Cd exposure and normalized pro-inflammatory cytokine levels.Cys also normalized the expression of Cd-disturbed lipid metabolism-related genes to improve lipid accumulation,which helped reduce liver damage.The treatment of Cys reduced oxidative stress and inflammatory responses,which may help to prevent Cd-induced lipid metabolism disorders and liver injury.