Shen Sheng, Zhou Jiexue, Meng Shandong, Wu Jiaqing, Ma Juan, Zhu Chunli, Deng Gengguo, Liu Dong
Department of Organ Transplantation, Guangdong Second Pronincial General Hospital, Guangzhou, Guangdong 510317, P.R. China.
Exp Ther Med. 2017 Nov;14(5):4077-4082. doi: 10.3892/etm.2017.5047. Epub 2017 Aug 28.
The aim of the present study was to investigate the protective effects of ischemic preconditioning on rats with renal ischemia-reperfusion injury and the effects on the expression of Bcl-2 and Bax. Thirty-six SD rats were randomly divided into three groups (n=12) including sham operation (S) group, ischemia-reperfusion group (I/R) group and ischemic preconditioning (IP) group. After anesthesia with intraperitoneal injection of chloral hydrate, bilateral renal pedicles were clipped for 45 min, followed by perfusion for 6 h to establish the I/R model. Both kidneys in rats of S group were separated and exposed for 45 min, but renal pedicles were not clipped. In IP group, bilateral renal pedicles were clipped for 5 min, followed by perfusion for 5 min, this procedure was repeated 3 times. Then bilateral renal pedicles were clipped for 45 min, followed by perfusion for 6 h. Blood samples were collected and rats were sacrificed to collect renal tissue. Levels of serum creatinine (Cr) and blood urea nitrogen (BUN) were measured. Activity of superoxide dismutase (SOD) was measured by xanthine oxidase assay. Degree of renal injury was evaluated by H&E staining. TUNEL kit was used to detect the number of apoptotic cells in renal tissue. Expression levels of Bcl-2 and Bax were detected by semi-quantitative PCR and western blot analysis at mRNA and protein levels, respectively. Results showed that levels of Cr and BUN in I/R and IP groups were significantly higher than those in S group, and levels of Cr and BUN in I/R group were significantly higher than that in IP group (P<0.05). Activity of SOD in I/R group and IP group were significantly lower than those in S group, and activity of SOD in I/R group were significantly lower than those in IP group (P<0.05). H&E staining showed that, compared with S group, renal injury in the I/R and IP groups was more serious than that in the S group, and I/R group was more serious than the IP group (P<0.05). TUNEL apoptosis assay showed that number of apoptotic cells in IP and I/R groups were significantly higher than that in the S group (P<0.01). Semi-quantitative PCR and western blot analysis showed that, compared with the S group, expression levels of Bcl-2 mRNA and protein were significantly decreased, expression levels of Bax mRNA and protein were significantly increased, and the ratio of Bcl-2/Bax was significantly decreased in the IP and I/R groups (P<0.01). Compared with the I/R group, expression level of Bcl-2 was significantly increased, the level of Bax was significantly deceased, and the ratio of Bcl-2/Bax was significantly increased in the IP group (P<0.01). As a result, ischemic preconditioning can protect rats with renal ischemia-reperfusion injury possibly by increasing the expression level of Bcl-2 and decreasing the expression level of Bax.
本研究的目的是探讨缺血预处理对肾缺血再灌注损伤大鼠的保护作用以及对Bcl-2和Bax表达的影响。将36只SD大鼠随机分为三组(n = 12),包括假手术(S)组、缺血再灌注(I/R)组和缺血预处理(IP)组。经腹腔注射水合氯醛麻醉后,夹闭双侧肾蒂45分钟,随后灌注6小时以建立I/R模型。S组大鼠的双侧肾脏分离并暴露45分钟,但不夹闭肾蒂。IP组先夹闭双侧肾蒂5分钟,随后灌注5分钟,此过程重复3次。然后夹闭双侧肾蒂45分钟,随后灌注6小时。采集血样并处死大鼠以收集肾组织。检测血清肌酐(Cr)和血尿素氮(BUN)水平。采用黄嘌呤氧化酶法检测超氧化物歧化酶(SOD)活性。通过苏木精-伊红(H&E)染色评估肾损伤程度。使用TUNEL试剂盒检测肾组织中凋亡细胞的数量。分别通过半定量PCR和蛋白质印迹分析在mRNA和蛋白质水平检测Bcl-2和Bax的表达水平。结果显示,I/R组和IP组的Cr和BUN水平显著高于S组,且I/R组的Cr和BUN水平显著高于IP组(P<0.05)。I/R组和IP组的SOD活性显著低于S组,且I/R组的SOD活性显著低于IP组(P<0.05)。H&E染色显示,与S组相比,I/R组和IP组的肾损伤比S组更严重,且I/R组比IP组更严重(P<0.05)。TUNEL凋亡检测显示,IP组和I/R组的凋亡细胞数量显著高于S组(P<0.01)。半定量PCR和蛋白质印迹分析显示,与S组相比,IP组和I/R组中Bcl-2 mRNA和蛋白质的表达水平显著降低,Bax mRNA和蛋白质的表达水平显著升高,且Bcl-2/Bax比值显著降低(P<0.01)。与I/R组相比,IP组中Bcl-2的表达水平显著升高,Bax水平显著降低,且Bcl-2/Bax比值显著升高(P<0.01)。因此,缺血预处理可能通过增加Bcl-2的表达水平和降低Bax的表达水平来保护肾缺血再灌注损伤的大鼠。