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目的观察铜负荷大鼠肝脏脂质过氧化损伤和凋亡的变化,探讨姜黄素对铜负荷大鼠肝脏的保护作用及其机制。方法建立铜负荷大鼠模型,应用姜黄素进行干预,分别检测干预前后肝组织匀浆的丙二醛(MDA)含量、超氧化物歧化酶(SOD)活力以及谷胱甘肽(GSH)含量,观察肝脏脂质过氧化损伤;电镜和原位末端脱氧核糖核苷酸转移酶分析法(TUNEL)观察大鼠肝脏凋亡改变;RT-PCR 检测大鼠肝组织肿瘤坏死因子(TNF-α)mRNA 和白介素8(IL-8)mRNA 的表达;酶联免疫吸附法检测肝组织匀浆 TNF-α和 IL-8含量。结果铜负荷组 MDA 值升高,SOD 及 GSH 值下降,凋亡指数从(2.2±1.2)%上升到(16.7±2.5)%,TNF-α和 IL-8 mRNA 的表达及蛋白含量高于正常组,与正常组相比差异均有统计学意义(P<0.01)。姜黄素组 MDA 值低于铜负荷组,SOD 及 GSH 值高于铜负荷组,凋亡指数从(16.7±2.5)%下降到(10.4±1.2)%,姜黄素组 TNF-α和 IL-8 mRNA 的表达及蛋白含量均低于铜负荷组,与铜负荷组相比差异有统计学意义(P<0.01)。电镜结果显示,姜黄素组大鼠肝脏线粒体肿胀、内质网扩张、溶酶体颗粒增多等改变轻于铜负荷组。结论过多的铜促进肝脏脂质过氧化损伤和诱导肝脏凋亡的发生,TNF-α和 IL-8参与铜对肝脏的损伤过程。姜黄素对铜负荷肝损伤有保护作用。
Objective To observe the changes of liver lipid peroxidation injury and apoptosis in copper-loaded rats, and to explore the protective effect and mechanism of curcumin on copper-loaded rat liver. Methods A rat model of copper stress was established and curcumin was used to intervene. The malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, and glutathione (GSH) content of liver homogenate before and after the intervention were measured. Hepatic lipid peroxidation injury was observed; electron microscopy and in situ terminal deoxyribonucleotidyl transferase assay (TUNEL) were used to observe the changes of rat liver apoptosis; RT-PCR was used to detect liver tumor necrosis factor-α (TNF-α) mRNA in rats. Expression of interleukin-8 (IL-8) mRNA; TNF-α and IL-8 contents in liver homogenate were detected by enzyme-linked immunosorbent assay. Results The MDA value in the copper stress group increased, and the SOD and GSH values decreased. The apoptotic index increased from (2.2±1.2)% to (16.7±2.5)%. The TNF-α and IL-8 mRNA expression and protein content were higher than normal. The difference between the group and the normal group was statistically significant (P<0.01). The MDA value in curcumin group was lower than that in copper stress group, the SOD and GSH values were higher than copper stress group, the apoptotic index decreased from (16.7±2.5)% to (10.4±1.2)%, and TNF-α and IL-8 in curcumin group. The mRNA expression and protein content were lower than those in the copper load group, and there was a statistically significant difference compared with the copper load group (P<0.01). The results of electron microscopy showed that changes in liver mitochondria, expansion of endoplasmic reticulum, and increase of lysosomal granules in the curcumin group were lighter than those in the copper load group. Conclusion Too much copper promotes lipid peroxidation in the liver and induces hepatic apoptosis. TNF-α and IL-8 participate in the process of copper injury to the liver. Curcumin has a protective effect on copper overload liver injury.