摘要目的：研究过表达富含半胱氨酸蛋白61（Cyr61）对缺血性急性肾损伤（AKI）早期肾组织细胞凋亡的影响及机制。方法30只SD大鼠被随机分为5组：对照组、AKI组、AKI＋碳酸氢盐组、AKI+空病毒组和AKI＋Cyr61过表达组。造模2 h后处死大鼠并留取血清和肾组织。采用ELISA法检测肾组织肿瘤坏死因子α（TNF?α）表达，HE染色观察各组肾组织病理改变，免疫组化法测定肾组织中核因子κB（NF?κB）p65和肿瘤坏死因子1型受体（TNFR1）的表达，原位末端转移酶标记技术（TUNEL）法检测肾组织细胞凋亡率，实时定量PCR法和 Western印迹法检测肾组织NF?κB p65、TNFR1和Caspase3 mRNA和蛋白的表达。结果与对照组相比，AKI组、AKI+碳酸氢盐组、AKI+空病毒组、AKI+Cyr61过表达组均出现明显肾组织损伤；肾组织TNF?α、NF?κB p65、TNFR1和Caspase3的mRNA和蛋白表达量明显增高（均P＜0.05）。与AKI组、AKI+碳酸氢盐组、AKI+空病毒组相比，AKI+Cyr61过表达组肾组织损伤程度、肾小管上皮细胞凋亡率、Scr增高幅度均明显降低（均P＜0.05）。AKI+Cyr61过表达组大鼠肾组织TNF?α表达与其他AKI阳性对照组相比差异无统计学意义，但NF?κB p65蛋白表达量降低，TNFR1和Caspase3蛋白表达增高程度较其他AKI阳性对照组减轻（均P＜0.05）。结论在缺血性AKI早期时，过表达Cy61的SD大鼠肾小管上皮细胞凋亡减轻，可能与Cy61蛋白抑制TNFR1的转录表达，干扰TNFα信号途径有关。

abstractsObjective To detect the effect and mechanism of Cyr61 on the apoptosis of renal tissue caused by early stage of ischemic acute kidney injury (AKI). Methods 30 SD rats were randomized into 5 groups, including control group, AKI group, AKI+bicarbonate group, AKI+blank virus group, and AKI+over?expression Cyr61 virus group. After animal models were created for 2h, serum and renal tissue were collected from sacrificed animals. Expression level of TNF?α was determined by ELISA. HE staining was used to observe the histologic changes of renal tissues. The levels of NF?κB p65 and TNFR1 were measured by immunohistochemical method. RT?PCR and Western blotting assay were adopted to detect the mRNA and protein expression levels of NF?κB p65, TNFR1 and Caspase3. Results Compared with control group, AKI group, AKI+bicarbonate group, AKI+blank virus group, AKI+over?expression Cyr61 virus group had obvious kidney injury. The levels of TNF?α, the mRNA and protein expression levels of NF?κB p65, TNFR1 and caspase3 were markedly up?regulated. Over?expression of Cyr61 significantly attenuated the degree of pathological injury, numbers of apoptotic renal tubular epithelial cells and increased the degree of Scr. Although compared with other groups, the level of TNF?α in kidney tissue had no difference, there was obvious decreased protein level of NF?κB p65, while the increase of TNFR1 and Caspase3 protein was moderate. Conclusions During the early stage of AKI, over expression of Cyr61 could inhibit apoptosis, which may be related to the suppression of TNFR1 transcriptional expression and interference of TNF?αpathway. Its underlying mechanism therefore deserves further research.