饮食模式对大鼠糖尿病早期肾脏病变的影响及其机制  

Effects of dietary patterns on early renal lesion in diabetic rats and its mechanisms

作　　者：李明 冯珊珊 金毅 黄宝明 贺碧霞 李玉 薛有安 王汝仙 谢泳娇 王茜 李静 LI Ming;FENG Shanshan;JIN Yi;HUANG Baoming;HE Bixia;LI Yu;XUE Youan;WANG Ruxian;XIE Yongjiao;WANG Qian;LI Jing(State Key Laboratory for Anti-infective Drug Development,Sunshine Lake Pharma Co.,Ltd,Dongguan 523871,China;Key Laboratory of Experimental Pathology of Guangdong Medical Products Administration,Shenzhen Institute for Drug Con-trol(Shenzhen Testing Center of Medical Devices),Shenzhen 518057,China)

机构地区：[1]广东东阳光药业股份有限公司,抗感染新药研发国家重点实验室,广东东莞523871 [2]深圳市药品检验研究院(深圳市医疗器械检测中心),广东省药监局实验病理学重点实验室,广东深圳518057

出　　处：《中国病理生理杂志》2023年第10期1832-1840,共9页Chinese Journal of Pathophysiology

基　　金：国家重点研发计划(No.2021YFF0702200;No.2021YFF0702204);抗感染新药研发国家重点实验室项目(No.2015DQ780357);广东省药品监督管理局实验病理学重点实验室项目(No.2020ZDB11);广东省基础与应用基础研究基金项目(No.2020A1515111061)。

摘　　要：目的:使用不同饮食模式联合链脲佐菌素(STZ)诱导建立大鼠糖尿病模型,确认模型结果并探索饮食模式对大鼠糖尿病早期肾脏病变的影响及其可能的机制。方法:将147只SD大鼠分别以正常饮食(维持饲料且自由摄食,n=25)、控制饮食(维持饲料但减量20%,n=25)和高脂饮食(高脂饲料且自由摄食,n=97)分组喂养后注射低剂量STZ,以空腹血糖是否达到糖尿病造模标准再分为未成模大鼠和成模大鼠,追踪动物的摄食、饮水和体重,通过组织病理学分析各组大鼠肾脏病变,采集各阶段的血浆样品并检测内源性代谢产物进而开展代谢组学分析。结果:不同饮食模式联合低剂量STZ可不同程度诱发大鼠糖尿病早期肾脏病变,主要表现为肾小管空泡变性,累及部分近曲小管和远曲小管。高脂饮食组的糖尿病成模率(89.2%)和肾脏病变率均最高(造模前期7/10,造模后期57/59),控制饮食组肾脏病变率最低(造模前期0/12,造模后期3/13)。相比正常饮食组,控制饮食组能量代谢和糖异生作用有关的代谢产物[如L-肉毒碱,不饱和脂肪酸二十四碳四烯酸(24:4n-6),氨基酸及其衍生物L-胱硫醚、4-氯-L-苏氨酸、L-酪氨酸等]有显著差异(P<0.05)。结论:高脂饮食可促进大鼠糖尿病及其肾脏病变的发生和发展;适当限制饮食量可促进大鼠的能量代谢和糖异生作用,有利于减轻大鼠糖尿病早期肾脏病变。AIM:To establish a rat diabetes model by streptozotocin(STZ)induction combined with different dietary patterns,and to investigate the effects of dietary patterns on early renal lesion in diabetic rats and its mechanisms.METHODS:Totally 147 SD rats were divided into regular diet group(conventional food,ad libitum;n=25),controlled diet group(conventional food,20%reduction in food amount;n=25)and high-fat diet group(high-fat food,ad libitum;n=97).After feeding for 70 d,all the rats were injected a low dose of STZ to establish rat diabetes model.According to the fasting blood glucose levels,non-diabetic rats and diabetic rats were also divided for analysis.The body weight,food in‐take and water intake of the rats were tracked,and the renal lesions were characterized by pathological alterations.Mean‐while,the rat plasma was sampled in each phase and the endogenous metabolites were analyzed by metabolomics approaches.RESULTS:Different dietary patterns combined with low-dose STZ induced early renal lesions in diabetic rats to different degrees.The main lesion was vacuolar degeneration of renal tubules,involving parts of proximal and distal convoluted tu‐bules.The rats in high-fat diet group exhibited the highest rates in both diabetes modeling(89.2%)and renal lesion+(7/10 and 57/59 in the early and late modeling period,respectively).The rats in controlled diet group showed the lowest re‐nal lesion+level(0/12 and 3/13 in the early and late modeling period,respectively).The plasma levels of several metabo‐lites in controlled diet group significantly changed(P<0.05)compared with regular diet group,such as L-carnitine,unsatu‐rated fatty acid[tetracosatetraenoic acid(24:4n-6)],and amino acid and their derivatives(L-tyrosine,L-cystathionine and 4-chloro-L-threonine),which were related to energy metabolism and gluconeogenesis.CONCLUSION:High-fat diet can significantly promote the occurrence and development of diabetes and diabetic renal lesion in rats.Proper dietary re‐striction may enhance energy metabolism and

关 键 词：糖尿病 早期肾脏病变 饮食模式 代谢组学 

分 类 号：R587.1[医药卫生—内分泌] R692[医药卫生—内科学] R459.3[医药卫生—临床医学]