利拉鲁肽对糖尿病肾病大鼠的肾保护作用及NLRP3炎症小体的影响

Renal protection of liraglutide on diabetic nephropathy rats and its effect on NLRP3 inflammasome

目的探讨利拉鲁肽对糖尿病肾病(DN)大鼠肾脏的保护作用及对NOD样受体3(NLRP3)炎症小体的影响。方法采用高糖高脂饮食联合小剂量链脲佐菌素建立大鼠DN模型,26只DN大鼠随机分为模型组和观察组,每组13只,同时取正常SD大鼠10只设为正常对照组。观察组予以利拉鲁肽400μg·kg-1皮下注射,每日1次,模型组和正常对照组给予等容量生理盐水皮下注射,连续给药8周。检测各组空腹血糖(FPG)、血尿素氮(BUN)、血肌酐(Scr)、血清白细胞介素1β(IL-1β)和白细胞介素18(IL-18)的水平以及24 h尿蛋白定量(UTP)。比较各组肾组织中NLRP3、凋亡相关斑点样蛋白(ASC)和天冬氨酸特异性半胱氨酸蛋白酶1(caspase-1)的蛋白和m RNA表达水平。结果模型组FPG、Scr、BUN、IL-1β、IL-18和UTP水平均高于正常对照组(P<0.05),观察组FPG、Scr、BUN、IL-1β、IL-18和UTP水平均低于模型组(P<0.05)。模型组肾组织中NLRP3、ASC、caspase-1蛋白和m RNA表达水平均高于正常对照组(P<0.05),观察组肾组织中NLRP3、ASC、caspase-1蛋白和m RNA表达水平均低于模型组(P<0.05)。结论利拉鲁肽对DN大鼠具有肾保护作用,该作用可能通过下调NLRP3炎症小体的表达而实现。

AIM To investigate renal protection of liraglutide on diabetic nephropathy（DN） rats and its effect on Nod-like receptor pyrin domain 3（NLRP3） inflammasome.METHODS DN model was induced by high glucose and high fat diet combined with small dose streptozotocin.Twenty-six DN rats were divided into model group and observation group by using random digital table,with 13 rats in each group.And 10 normal rats were selected as normal control group.The observation group was given liraglutide 400 μg·kg-1 subcutaneous injection,once a day.The model group and normal control group were given normal saline subcutaneous injection.The drug was given for 8 weeks.The fasting plasma glucose（FPG）,serum creatinine（Scr）,blood urea nitrogen（BUN） and 24 h urinary total protein（UTP） were detected by automatic biochemistry analyzer.The expression of interleukin-1 beta（IL-1β） and interleukin-18（IL-18） in serum was detected by ELISA.The expression of NLRP3,apoptosis-associated speck-like protein containing CARD（ASC）,caspase-1 protein and m RNA were detected by Western blot and reverse transcriptase polymerase chain reaction（RT-PCR）.RESULTS The levels of FPG,Scr,BUN,IL-1β,IL-18 and UTP in the model group were significantly higher than those in the normal control group（P〈0.05）.The levels of FPG,Scr,BUN,IL-1β,IL-18 and UTP in the observation group were significantly lower than those in the model group（P〈0.05）.The levels of NLRP3,ASC,caspase-1 protein and m RNA in the renal tissue of the model group were higher than those in the normal control group with statistical difference（P〈0.05）.The levels of NLRP3,ASC,caspase-1 protein and m RNA in the renal tissue of the observation group were lower than those in the model group with statistical difference（P〈0.05）.CONCLUSION Liraglutide has renal protective effect on DN rats,and the effect may be achieved through down-regulation of NLRP3 inflammasome.