长程高脂饲料对雌雄大鼠非酒精性脂肪肝差异的影响及机制的初步探讨

Gender Difference of Non-Alcoholic Fatty Liver in Sprague-Dawley Rats Induced by Long-Term High-Fat Diet

目的观察SD雌雄大鼠肝脏脂质沉积情况,探讨形成雌雄大鼠脂肪肝差异的可能机制。方法肝脏组织石蜡切片HE染色,用光镜观察肝脏脂质沉积情况。测定第14个月大鼠肝脏组织甘油三酯水平。测定第14个月大鼠的空腹血糖和空腹胰岛素,计算胰岛素抵抗指数。测定第14个月大鼠肝脏组织匀浆液中线粒体和微粒体的丙二醛和过氧化氢酶的含量,检测大鼠肝脏组织氧化应激和抗氧化应激水平。结果①长程高脂喂养14个月后雌雄大鼠高脂组肝脏组织出现弥散性的脂肪滴沉积,但无明显的炎性细胞浸润,未见纤维化形成,也未观察到明显的局部性肝细胞坏死或细胞凋亡等现象;②雄性高脂组大鼠肝脏组织的脂肪泡比雌性大鼠的面积大并且数量多,且雄性高脂组肝脏甘油三酯水平显著高于雌性高脂组(P<0.001);③第14个月,雌雄大鼠空腹血糖水平无显著差异,高脂雄性大鼠空腹胰岛素水平显著高于高脂雌性大鼠(P<0.05)。高脂雄性大鼠胰岛素抵抗水平(HOMA-IR)亦显著高于高脂雌性大鼠(P<0.05);④雌性高脂组大鼠肝脏组织中丙二醛水平都低于雄性大鼠高脂组,过氧化氢酶水平都高于雄性高脂组大鼠,有显著性差异(P<0.05)。结论单纯长程高脂饲料喂养SD雌雄大鼠能引起典型的脂肪肝的形成,并且雄性高脂组大鼠脂肪肝的程度比雌性高脂组严重,其机制可能与雌性大鼠的外周胰岛素抵抗水平和肝脏组织的氧化应激水平低于雄性大鼠有关。

Objective In this study, we examined the long-term influence of a high-fat （HF） diet, compared to a control chow diet, on fatty liver in genetically normal Sprague-Dawley （SD） rats. Fourteen-monthS feeding represents almost a life-long exposure of the rats to the diet. Methods One hundred SD rats were equally divided by gender and further grouped into standard laboratory chow （SC） and HF groups. Lipid deposition in liver was observed using paraffin section and HE staining. At the 14^th month, fasting plasma glucose and insulin concentrations were measured. Insulin resistance （HOMA-IR） was calculated according to homeostasis model assessment, and liver triglyceride （TG） was also measured. Meanwhile, the concentrations of malondialdehyde （MDA） and catalase （CAT） in liver were determined to evaluate the oxidant and antioxidant capabilities. Results ① Histological evaluation of liver by HE staining showed extensive TG accumulation in HF rats, but neither penetrative inflammatory ceils nor fibrosis were observed. ② In the liver of HF male rats, lipid droplet was bigger and more extensively distributed than that in the lever of HF female rats. Consistently, the amount of TG was significantly higher compared with HF female rats （P 〈0. 001 ） . In contrast, no difference was observed between either gender of SC rats. ③ Fast insulin levels in HF-fed male rats were significantly higher than that of age-matched female rats （P 〈 0. 05 ）, and HOMA-IR was statistically different between HF-fed groups as well at 14th month （P 〈 0. 05）, whereas no significant differences were observed between two sexes under SC condition. ④While the level of MDA significantly increased, the levels of CAT dramatically decreased in the liver of HF-fed male rats, as compared with HF-fed female rats （P 〈0.05 -0.01 ） . Conclusion These findings demonstrate that long-term high-fat feeding leads to fatty liver in SD rats, with more severe effect on males than females. The decline of both peripheral insulin resistance and liver oxidative stress in female rats might contribute to these gender-related differences.