C型钠尿肽对肾缺血再灌注大鼠肾功能和肾组织细胞凋亡的影响及机制

发布时间：2019-04-24 19:31

【摘要】：目的观察C型钠尿肽(CNP)对肾缺血再灌注损伤大鼠肾功能、肾组织细胞凋亡的影响,并探讨其机制。方法将24只雄性Wistrar大鼠随机分为Sham组、IR组和CNP组,每组8只。各组大鼠均摘除左侧肾脏,IR组和CNP组用无创性小血管夹夹闭右肾动静脉,45 min后取下血管夹恢复肾脏血供,并分别于夹闭右肾动静脉的同时即刻持续缓慢输注生理盐水约2 mL、CNP 0.2μmol/(kg·min)至再灌注2 h;Sham组不夹闭右肾动静脉。再灌注24 h后取血测定血清肌酐(Cr)、尿素氮(BUN),取右肾以ELISA法测定肾组织环磷酸鸟苷(cGMP),TUNEL染色检测肾脏织的凋亡细胞,Western blot法检测肾脏组织蛋白激酶B(Akt)和β糖原合成酶激酶3β(GSK-3β)蛋白及其磷酸化蛋白。结果与Sham组比较,IR组大鼠血清Cr和BUN水平均升高(P均0.01),肾组织cGMP浓度降低、细胞凋亡率升高(P均0.05),肾组织中Akt、GSK-3蛋白磷酸化水平均降低(P均0.01);与IR组比较,CNP组大鼠血清Cr和BUN水平均降低(P均0.05),肾组织cGMP浓度升高、细胞凋亡率降低(P均0.05),肾组织中Akt、GSK-3蛋白磷酸化水平均升高(P均0.01)。结论 CNP减轻肾脏缺血再灌注大鼠肾功能损伤及肾脏组织细胞凋亡,其机制可能与提高肾组织cGMP水平,进而提高Akt和GSK-3β蛋白磷酸化有关。
[Abstract]:Aim to observe the effect of C-type natriuretic peptide (CNP) on renal function and apoptosis of renal tissue in rats with renal ischemia-reperfusion injury and to explore its mechanism. Methods Twenty-four male Wistrar rats were randomly divided into three groups: Sham group, IR group and CNP group, with 8 rats in each group. The left kidney was removed in each group. The right renal arteriovenous clamp was used in IR group and CNP group. After 45 min, the renal blood supply was restored. 2 mL,CNP 0.2 渭 mol / (kg 路min) saline was infused to reperfusion for 2 h at the same time of occlusion of right renal arteriovenous system. The right renal artery and vein were not occluded in Sham group. 24 hours after reperfusion, serum creatinine, (Cr), urea nitrogen, (BUN), were taken from the right kidney and ELISA method was used to detect the apoptotic cells in renal tissue by cyclic guanosine phosphate (cGMP), TUNEL staining. Renal protein kinase B (Akt) and 尾 glycogen synthase kinase 3 尾 (GSK-3 尾) proteins and their phosphorylated proteins were detected by Western blot. Results compared with Sham group, the levels of serum Cr and BUN in IR group were higher than those in control group (P0.01), the concentration of cGMP in renal tissue was decreased, the apoptosis rate was increased (P0.05), and Akt, in renal tissue was increased (P0.05). The phosphorylation level of GSK-3 protein was lower than that of control group (P0.01). Compared with IR group, the levels of serum Cr and BUN in CNP group were lower, the concentration of cGMP in kidney tissue was higher, the apoptosis rate was lower (all P 0.05), and Akt, in renal tissue was decreased (all P 0.05). The phosphorylation level of GSK-3 protein was increased (P0.01). Conclusion CNP can reduce renal function injury and apoptosis of renal tissue in rats with renal ischemia / reperfusion. The mechanism may be related to the increase of cGMP level in renal tissue and the increase of phosphorylation of Akt and GSK-3 尾 protein.
【作者单位】：延边大学附属医院;延边大学医学院;
【基金】：国家自然科学基金资助项目(81460056)
【分类号】：R692

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