目的:研究有氧运动对自发性高血压大鼠(spontaneously hypertensive rats,SHR)肾脏内细胞焦亡相关蛋白表达的影响,探讨有氧运动对自发性高血压大鼠肾损害的作用.方法:8周龄雄性SHR和Wistar京都大鼠(wistar-kyoto rat,WKY),随机分为4组(n=6):安静组(WKY)、高血压安静组(SHR-N)、低强度有氧运动组(SHR-L)、中强度有氧运动组(SHR-M).SHR-L组和SHR-M组分别在0°坡度的运动跑步机上以12~14 m/min和18~20 m/min进行有氧运动,每周5次,每次60 min,WKY和SHR-N安静饲养.10周后,训练结束72 h后检测血压.检测血清肌酐(creatinine,Cr)、尿素氮(urea nitrogen,BUN).Masson染色观测肾脏病理学改变,并将肾脏功能指标(index of renal function,RFI)作为肾功能损伤指标.测定大鼠肾组织中核苷酸结合寡聚化结构域样受体蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)、含半胱氨酸的天冬氨酸蛋白水解酶 1(cysteinyl aspartate specific proteinase,Caspase-1)、cleaved-Caspase-1、Toll样受体4(Toll Like Receptor 4,TLR4)、IL-1β、IL-18、Gasdermin D、GSDMDC1等蛋白表达.检测血清中IL-1β和IL-18表达.结果:与WKY相比,SHR-N血压、血清Cr、BUN 含量、RFI 比值、NLRP3、Caspase-1、TLR4、IL-1β、IL-18、GSDMD、GSDMDC1 蛋白、血清中 IL-1β 和 IL-18 表达升高;与SHR-N 相比,SHR-M 血压、血清 Cr、BUN 含量、RFI 比值以及 NLRP3、Caspase-1、TLR4、IL-1β、IL-18、GSDMD、GSDMDC 1 蛋白表达下降明显,而SHR-L组下降趋势不明显.结论:有氧运动强度差异与自发性高血压大鼠肾脏NLRP3炎症小体表达、血压以及肾功能损害均具有统计学意义.与低强度有氧运动相比,中强度有氧运动通过TLR4/NLRP3信号通路改善自发性高血压大鼠肾功能损害更明显.
Effects of different intensities of aerobic exercise on the kidney of spontaneously hypertensive rats
Objective:To study the effects of aerobic exercise on the expression of pyroptosis-related proteins in the kidney of sponta-neously hypertensive rats(SHRs),and to explore the effects of aerobic exercise for hypertensive renal damage in SHRs.Methods:Eight-week-old male SHRs and Wistar Kyoto rats(WKYs)were randomly divided into four groups(n=6 in each group):control group(WKY),non-exercise hypertension group(SHR-N),low-intensity aerobic exercise hypertension group(SHR-L),and moderate-intensity aerobic exercise hypertension group(SHR-M).The rats in the SHR-L and SHR-M groups were subjected to running on a sports treadmill at a slope of 0° at 12-14 m/min and 18-20 m/min for 60 min,respectively,for 5 times per week.The WKY and SHR-N groups had no exercise intervention.After 10 weeks,72 hours after exercise,we measured the blood pressure of rats;measured serum creatinine(Cr),urea nitrogen(BUN),interleukin(IL)-1β,and IL-18;observed the pathological changes in the kidney with Masson staining,and calculated the renal function index(RFI)to reflect the severity of renal function impairment;and measured the protein ex-pression of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),cysteinyl aspartate-specific proteinase 1(cas-pase-1),cleaved caspase-1,toll-like receptor 4(TLR4),IL-1β,IL-18,gasderm in D(GSDMD),and GSDMDC1 in the renal tissue of rats.Results:Compared with the WKY group,the SHR-N group showed significant increases in blood pressure,serum Cr,BUN,IL-1β,and IL-18 levels,and RFI,as well as the expression of NLRP3,caspase-1,TLR4,IL-1β,IL-18,GSDMD,and GSDMDC1 in the kidney.Compared with the SHR-N group,the SHR-M group showed significantly decreased blood pressure,serum Cr and BUN,and RFI,as well as NLRP3,caspase-1,TLR4,IL-1β,IL-18,GSDMD,and GSDMDC1,while the SHR-L group had no significant re-ductions.Conclusion:Different intensities of aerobic exercise produce varying degrees of effects on renal NLRP3 inflammasome ex-pression,blood pressure,and renal function in SHRs.Moderate-intensity aerobic exercise is superior to low-intensity aerobic exercise in improving renal function in SHRs through the TLR4/NLRP3 signaling pathway.
nucleotide-binding oligomerization domain-like receptor protein 3spontaneously hypertensive ratkidneyaerobic exer-ciseexercise intensity