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富硒灵芝粗提物对2型糖尿病模型大鼠脂代谢、肝功能及炎症反应的改善作用研究
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| 篇名： | 富硒灵芝粗提物对2型糖尿病模型大鼠脂代谢、肝功能及炎症反应的改善作用研究 |
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| 摘要： | 目的：研究富硒灵芝粗提物对2型糖尿病（T2DM）模型大鼠脂代谢、肝功能及炎症反应的改善作用。方法：将120只大鼠随机分为正常对照组（n＝20，生理盐水）和造模组（n＝100）。正常对照组大鼠喂养普通饲料，造模组大鼠喂养高脂饲料。4周后，造模组大鼠腹腔注射链脲佐菌素溶液（30 mg/kg）复制T2DM模型。将造模成功的90只大鼠再次随机分为模型对照组（生理盐水）、阳性对照组（二甲双胍，200 mg/kg）和富硒灵芝粗提物低、中、高剂量组（300、600、1 200 mg/kg，以提取物计），每组18只。灌胃给药，每天1次，每周周一至周六给药。分别于给药4、8周后各组均取一半大鼠，检测其血清中葡萄糖、胰岛素水平，并计算胰岛抵抗指数；采用酶联免疫吸附法检测其血清中肝功能指标[天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、碱性磷酸酶（AKP）]、血脂指标[游离脂肪酸（FFA）、总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）]和炎症因子[肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）、IL-1β]水平；苏木精-伊红染色后，通过显微镜观察其肝组织病理学变化；并分别采用实时荧光定量-聚合酶链式反应法和Western blot法检测其肝组织中过氧化物酶体增殖物激活受体α（PPARα）、过氧化物酶酰基辅酶A 氧化酶1（ACOX1）的mRNA和蛋白表达水平。结果：与正常对照组比较，模型对照组大鼠在给药4、8周后血清中葡萄糖、胰岛素含量显著增加（P＜0.01），胰岛素抵抗指数显著升高（P＜0.01）；血清中肝功能指标、血脂指标和炎症因子水平均显著升高（P＜0.05或P＜0.01）；肝细胞肿胀呈圆形，且体积较正常对照组明显增大，肝脏有不同程度的脂肪变性及空泡样变，并伴随有少量炎细胞浸润现象；肝组织中PPARα、ACOX1的mRNA和蛋白表达水平显著降低（P＜0.05或P＜0.01）。与模型对照组比较，除富硒灵芝粗提物低剂量组大鼠给药4周后的胰岛素抵抗指数和血清中AST、ALT、IL-6、IL-1β水平以及给药8周后血清中葡萄糖、胰岛素、ALT水平和给药4、8周后4个血脂指标水平降低不显著外（P＞0.05），其余各组大鼠在给药4、8周后上述血清指标水平均显著降低（P＜0.05或P＜0.01）；给药4、8周后大鼠肝组织病理学变化不同程度减轻；各给药组大鼠给药4、8周后肝组织中PPARα、ACOX1的蛋白和mRNA表达水平均显著升高（P＜0.05或P＜0.01）。结论：富硒灵芝粗提物可上调肝组织中PPARα和ACOX1蛋白和mRNA的表达，促进蓄积的脂肪酸排出，明显改善T2DM模型大鼠脂肪酸代谢、炎症反应和肝功能。 |
| ABSTRACT： | OBJECTIVE： To study the effects of selenium-enriched Ganoderma lucidum crude extract on lipid metabolism， liver function and inflammatory response in type 2 diabetic model rats. METHODS： Totally 120 rats were randomly divided into normal control group （n＝20， normal saline） and model group （n＝100）. Normal control group was fed with normal diet， and model group was fed with high-fat diet. 4 weeks later， model group was given intraperitoneal injection of Streptozotocin solution （30 mg/kg） to induce T2DM model. After modeling， 90 rats were randomly subdivided into model control group （normal saline）， positive control group （metformin， 200 mg/kg） and selenium-enriched G. lucidum crude extract low-dose， medium-dose and high-dose groups （300， 600， 1 200 mg/kg， calculated by extract）， with 18 rats in each group. They were given medicine intragastrically， once a day， from Monday to Saturday. Half of rats in each group were selected 4， 8 weeks after medication； the serum levels of glucose and insulin were detected， and islet resistance index were calculated. The serum levels of liver function indexes （AST， ALT， AKP）， blood lipid indexes （FFA， TC， TG， LDL-C） and inflammatory factors （TNF-α， IL-6， IL-1β） were detected by ELISA. After HE staining， the histopathological changes of liver tissue were observed by microscopy. mRNA and protein expressions of peroxisome proliferator activated receptor α （PPARα） and peroxidase acyl coenzyme A oxidase 1 （ACOX1） in liver tissue were detected by RT-qPCR and Western blot assay. RESULTS： Compared with normal control group， glucose， insulin serum levels and islet resistance index were significantly increased （P＜0.01）； serum liver function indexes， blood lipid indexes and inflammatory factor levels of model control group were increased significantly in model control group after 4 and 8 weeks medication （P＜0.05 or P＜0.01）. The hepatocyte swelling of model control group was round and the volume was significantly larger than that of blank control group. The liver had different degrees of steatosis and vacuolization， accompanied by a small amount of inflammatory cell infiltration. mRNA and protein expressions of PPARα and ACOX1 in liver tissue were decreased significantly （P＜0.05 or P＜0.01）. Compared with model control group， except that there was no significant decreased in islet resistunce index and AST， ALT， IL-6， IL-1β serum levels after 4 weeks of medication， and glucose， insulin， ALT serum levels after 8 weeks of medication and the levels of 4 blood lipid indexes after 4 and 8 weeks of medication in selenium-enriched G. lucidum crude extract low-dose group （P＞0.05）， above serum indexes of other groups were decreased significantly after 4 and 8 weeks of medication （P＜0.05 or P＜0.01）. After 4 and 8 weeks of medication， the pathological changes of liver tissue in rats were alleviated in varying degrees. protein and mRNA expressions of PPARα and ACOX1 in liver tissue were increased significantly after 4 and 8 weeks of medication （P＜0.05 or P＜0.01）. CONCLUSIONS： Selenium-enriched G. lucidum crude extract can up-regulate protein and mRNA expressions of PPARα and ACOX1 in liver tissue， promote the excretion of accumulated fatty acid and significantly improve fatty acid metabolism， inflammatory response and liver function in T2DM model rats. |
| 期刊： | 2019年第30卷第3期 |
| 作者： | 杨丹阳，姜涛，周径，张雪杨 |
| AUTHORS： | YANG Danyang，JIANG Tao，ZHOU Jing，ZHANG Xueyang |
| 关键字： | 富硒灵芝粗提物；2型糖尿病；过氧化物酶体增殖物激活受体α；过氧化物酶酰基辅酶 A氧化酶1；大鼠 |
| KEYWORDS： | Selenium-enriched Ganoderma lucidum crude extract； Type 2 diabetes mellitus； Peroxisome proliferator activated receptor α； Peroxidase acyl coenzyme A oxidase 1； Rat |
| 阅读数： | 246 次 |
| 本月下载数： | 3 次 |
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