灵芝多糖对非酒精性脂肪肝大鼠PPARγ和环氧合酶-2表达的影响

Effects of Ganoderma lucidum polysaccharides on the PPAR γ and COX-2 in the rat with non-alcoholic fatty liver disease

目的:探讨灵芝多糖(GLPs)对非酒精性脂肪肝大鼠的防治作用及其对过氧化物酶体增殖物激活受体γ(PPARγ)和环氧合酶-2(COX-2)表达的影响。方法:SD大鼠72只随机分为6组,每组12只,正常对照组(N组),模型组(M组),灵芝多糖低、中、高剂量组(GLPs-L、GLPs-M、GLPs-H组)和辛伐他汀组(SV组)。用高脂饲料喂养建立大鼠非酒精性脂肪肝模型。经12周给药后,分别测定各实验组ALT、AST、脂联素和肿瘤坏死因子-α的含量;透射电镜观察肝组织超微结构;用逆转录聚合酶链反应法和Western Blot检测肝组织中PPARγ和COX-2 mRNA和蛋白的表达情况。结果:(1)灵芝多糖中、高剂量组血清ALT、AST和肿瘤坏死因子-α含量显著降低,而脂联素含量则明显升高(P<0.05或P<0.01),差异均有统计学意义;(2)肝组织病理学结果显示,M组大鼠肝组织中充满大小不等的脂滴,线粒体肿胀,染色体边集等;(3)M组肝组织PPARγmRNA和蛋白的表达显著降低(P<0.05或P<0.01),而COX-2 mR-NA和蛋白的表达显著升高(P<0.01),灵芝多糖中、高剂量组PPARγmRNA和蛋白的表达显著升高(P<0.05或P<0.01),同时COX-2 mRNA和蛋白的表达显著降低(P<0.05或P<0.01),差异均有统计学意义。结论:灵芝多糖能改善胰岛素抵抗,降低炎症因子的表达,对非酒精性脂肪肝有一定的防治作用。

Objective： To investigate the protective effects of ganoderma lucidum polysaccharides （GLPs） on the ex- pressions of PPAR γ and COX-2 in the rat with non-alcoholic fatty liver disease. Methods： Seventy-Two SD rats were randomly divided into six groups： the normal group（NG）, the model group（MG）, the Ganoderma lucidum polysaccharides of low, middle and high-dose group （GLPs-LG, GLPs-MG, GLPs-HG） and the Simvastatin group （SV）. The rats were fed with high fat diet. At 12th weekend, the following indices of rats in each group were measured respectively： the serum levels of alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, adiponectin and tumor necrosis factor-alpha （TNF-α）; Histopathological changes of rat liver were observed under electron microscope; The mRNA and protein expressions of pei- oxisome proliferator-activated receptor γ（PPARγ） and cyclooxygenase-2（COX-2） were assessed by RT-PCR and western blot. Results： ALT, AST and TNF-α were decreased after GLPs treatment, while adiponectin was increased （P〈0.05 或 P〈 0.01）. Meanwhile, the histological evaluation demonstrated that GLPs dramatically ameliorate uhrastructure in liver tissue. Importantly, the level of PPAR γ mRNA and protein were increased （P〈0.05 或 P〈0.01）, while the level of COX-2 mRNA and protein were decreased after GLPs treatment （P〈0.05 或 P〈0.01）. Conclusion： GLPs could improve insulin resistance effectively and reduce expression of inflammatory cytokines, and thus it has good preventive effect on non-alcoholic fatty liver disease rats.