粗毛纤孔菌提取物对高尿酸血症小鼠的降尿酸及肝肾保护作用

Effects of Inonotus hispidus fruiting body extracts on reducing uric acid and protecting liver and kidney of hyperuricemia mice

探究粗毛纤孔菌提取物对高尿酸血症(hyperuricemia,HUA)小鼠的降尿酸效果及对肝肾的保护作用。腹腔注射氧嗪酸钾联合灌胃次黄嘌呤建立HUA小鼠模型,灌胃粗毛纤孔菌石油醚提取物(高剂量组12mg/kg、低剂量组6mg/kg)、粗毛纤孔菌水提物(高剂量组624mg/kg、低剂量组312 mg/kg)及麦角甾醇(高剂量组10 mg/kg、低剂量组5 mg/kg)进行干预,检测肝脏及肾脏指数、小鼠血清指标尿酸(uric acid,UA)、肌酐(creatinine,CRE)、尿素氮(blood urea nitrogen,BUN)、血清和肝脏中黄嘌呤氧化酶(xanthine oxidase,XOD)和腺苷脱氨酶(adenosine deaminase,ADA)活力、肾脏中肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)和白细胞介素-1β(1L-1β)含量,并用苏木精-伊红染色法观察肝、肾组织的病理学特征,免疫组化及蛋白印迹法(western blotting)实验观察肾脏中三磷酸腺苷结合转运蛋白(ATP-binding cassette subfamily G member2,ABCG2)、葡萄糖转运蛋白9(glucose transporter 9,GLUT9)、NLRP3炎症小体(NLR family pyrin domain containing 3,NLRP3)定位表达及表达水平。与模型组相比,粗毛纤孔菌提取物均可显著降低小鼠肝脏和肾脏指数,显著下调血清UA、CRE、BUN水平,石油醚提取物高剂量组、麦角甾醇组分别显著下调血清中XOD、ADA活力,石油醚提取物组和麦角甾醇组均可显著下调肝脏中XOD、ADA活力及TNF-α、1L-1β含量。水提取物高剂量组、石油醚提取物高剂量组、麦角甾醇高剂量组可显著修复HUA小鼠损伤的肝脏和肾脏。粗毛纤孔菌石油醚提取物高剂量组、麦角甾醇高剂量组可显著上调ABCG2的蛋白表达,下调GLUT9、NLRP3表达水平。粗毛纤孔菌石油醚提取物及麦角甾醇对HUA小鼠有显著的降尿酸和肝肾保护作用,为进一步开发利用粗毛纤孔菌提供参考。

The hyperuricemia(HUA)mouse model was established by intraperitoneal injection of potassium oxazinate combined with hypoxanthine.Petroleum ether extract(12 mg/kg for high-dose group and 6 mg/kg for low-dose group)and water extract(624 mg/kg for high-dose group and 312 mg/kg for low-dose group)of Inonotus hispidus fruiting bodies and ergosterol(10 mg/kg for high-dose group and 5 mg/kg for low-dose group)were given orally.The indexes of liver and kidney,serum indexes(uric acid,UA;creatinine,CRE;blood urea nitrogen,BUN)of mice,the activities of xanthine oxidase(XOD)and adenosine deaminase(ADA)in serum and liver,tumor necrosis factor-α(TNF-α)and 1L-1βcontent in kidney were detected.The pathological features of liver and kidney were observed by hematoxylin-eosin staining,and the localized expression and expression levels of ABCG2,GLUT9 and NLRP3 in kidney were observed by immunohistochemistry and western blotting experiments.Compared with the model group,the extracts of I.hispidus fruiting bodies can significantly reduce the indexes of liver and kidney,and significantly reduce the levels of UA,CRE and BUN in serum of HUA mice.The activities of XOD and ADA in serum were significantly decreased in the high-dose treatment group of mice orally taking petroleum ether extract and ergosterol,and the activities of XOD and ADA and the content of TNF-αand 1L-1βin liver were significantly decreased in both treatment groups.The treatments of high-dose water extract,high-dose petroleum ether extract and high-dose ergosterol can significantly repair the damaged liver and kidney of HUA mice.Taking high-dose petroleum ether extract and high-dose ergosterol can significantly up-regulate the protein expression of ABCG2 and down-regulate the expression levels of GLUT9 and NLRP3 of HUA mice.This study comes to the conclusion that petroleum ether extract of I.hispidus fruiting bodies and ergosterol have significant effects on reducing uric acid and protecting liver and kidney in HUA mice,and further development and utilization of I.hispidus as new Chinese medicine is needful.