肝脏线粒体呼吸功能损伤在大鼠非酒精性脂肪性肝病中的作用

Effect of structural and functional damages in hepatic mitochondria on genesis of NAFLD

目的探讨大鼠非酒精性脂肪性肝病(NAFLD)形成过程中肝脏线粒体形态和功能的损伤以及在NAFLD形成中的可能作用。方法基础饮食与高脂饮食制作正常对照组(C组)与非酒精性脂肪性肝病组(F组)模型,每组设立4、8、12周3个时相点,分别用Clark氧电极检测肝脏线粒体呼吸功能,荧光分光光度计测定线粒体膜电位;硫代巴比妥酸法测定肝脏组织丙二醛(MDA)的含量变化。结果F组逐渐出现肝脂肪变,且饲养时间越长,肝脏脂肪变程度越重,并在F12周组出现脂肪性肝炎,而C组大鼠肝脏病理正常;F组大鼠肝脏线粒体RCR(呼吸控制率)、P/O(磷/氧比值)比值随饲养时间的延长逐渐下降,F组4周与C组4周差异无统计学意义,而F组8、12周与相应时相C组比较,RCR显著降低,差异有统计学意义(P<0.05、P<0.01),F组4、8、12周P/O比值较C组相应时相点均降低,差异有统计学意义(P<0.05、P<0.01);第4周后肝脏内MDA含量在F组明显高于对照组,差异有统计学意义(P<0.05),随饲养时间延长,F组MDA逐渐增加。结论肝脏线粒体功能损伤在NAFLD发病机制中起关键作用,肝脏脂肪变程度越重,其线粒体功能损伤越明显。

Objective To investigate the structural and functional damages of hepatic mitochondria and their effect on nonalcoholic fatty liver disease（NAFLD） in rats. Methods A total of 36 Wistar rats were randomly divided into basic diet-control group （group C） and high-fat diet group （group F）. Each of the two groups was subdivided into 3 subgroups （4,8,12 weeks,6 cases in each group）. Respiratory chain function of mitochondria was detected by Clark oxygen electrode, and mitochondrial membrane potential by fluorescence spectrophotometer, levels of malondialdehyde （MDA） in liver tissue detected by using thio-barbituric acid. Results Respiratory control rates （RCR） in group F at 8 week （3.87±0.44） and 12 week （3.51±0.18） were significantly lower than those in group Cat 8week （4.93±0.79） and 12 week （4.85±0.47） （P〈0.05, P〈0.01）. P/O in group F at 4week （3.61±0.39）, 8 week （3.56±0.34）, and 12 week （3.37±0.25） were significantly lower than those in group C at 4 week （4.22±0. 63）, 8 week （4. 11±0.29）, and 12 week （4.13±0.39） （P〈0.05 orP〈0.01）. Mitochondrial membrane potentials in group F at 4 week （833.1±53.5）, 8 week （772.2±73.4）, and 12 week （587.2±63.1） were significantly lower than those in group C at 4 week （951.2±64.6）, 8 week （977.2±78.3）, and 12 week （958.6±70.4） （P〈0.05 or P〈0.01）. Liver tissue MDA levels in group F were significantly higher than those in group C （P〈0.05）. Conclusion Structural and functional damages in hepatic mitochondria occur in the genesis and progression of NAFLD.