胰激肽原酶对他克莫司诱导的大鼠肾脏损伤的保护作用  

Protective effect of pancreatic kininogenase on tacrolimus-induced kidney injury in rats

作　　者：张隆业 刘维萍[1] 张彦芬[1] 郭永力[1] 管仁苹 邵雪 王兆宇 李灿[2] Zhang Longye;Liu Weiping;Zhang Yanfen;Guo Yongli;Guan Renping;Shao Xue;Wang Zhaoyu;Li Can(Department of Nephrology,First Hospital of Qinhuangdao City,Qinhuangdao 066000,Hebei Province;Affiliated Hospital of Yanbian University,Yanji 133000,Jilin Province,China)

机构地区：[1]秦皇岛市第一医院肾内科,066000 [2]延边大学附属医院,延吉市133000

出　　处：《中华肾病研究电子杂志》2021年第4期198-204,共7页Chinese Journal of Kidney Disease Investigation（Electronic Edition）

基　　金：秦皇岛市科学技术研究与发展计划(201902A179)。

摘　　要：目的探讨胰激肽原酶(PK)对他克莫司(TAC)诱导的肾脏损伤大鼠的保护作用。方法48只Sprague-Dawley成年雄性大鼠,随机分为4组,每组12只:(1)对照(vehicle,VH)组:腹腔注射橄榄油1 ml/(kg·d)和生理盐水2 ml/(kg·d);(2)VH+PK组:腹腔注射橄榄油1 ml/(kg·d)和PK7.2 U/(kg·d);(3)TAC组:腹腔注射生理盐水2 ml/(kg·d)和TAC 1.5 ml/(kg·d);(4)TAC+PK组:腹腔注射PK 7.2 U/(kg·d)和TAC 1.5 mg/(kg·d)。各组分别连续给药4周后处死大鼠,收集血液、尿液及肾组织标本;检测各组大鼠的一般生化指标、肾功能;病理观察评价肾间质纤维化;采用ELISA和Western印迹检测炎性因子、致纤因子以及抗氧化剂的表达,采用ELISA检测氧化性DNA标志物。结果与VH组相比,TAC组的血肌酐(Scr)、血尿素氮(BUN)、肾间质纤维化程度、转化生长因子-β1(TGF-β1)和白介素6(IL-6)的表达、血清和尿液8-羟化脱氧鸟苷(8-OHdG)的含量、单核巨噬细胞抗原-1(ED-1)和骨桥蛋白(OPN)的阳性表达细胞均显著增加(P<0.05),而锰超氧化物歧化酶(MnSOD)的表达显著降低(P<0.05)。与TAC组相比,TAC+PK组的Scr、BUN、肾间质纤维化程度、TGF-β1和IL-6的表达、血清和尿液8-OHdG的含量、ED-1和OPN的阳性表达细胞均显著减少(P<0.05),而MnSOD的表达显著增加(P<0.05)。结论PK治疗能够减轻TAC引起的肾功能不全、肾间质纤维化、间质性炎症和氧化应激。PK治疗可能对TAC诱导的肾脏损伤具有保护作用。Objective To investigate the protective effect of pancreatic kininogenase(PK)on tacrolimus(TAC)-induced kidney injury in rats.Methods 48 adult male Sprague-Dawley rats were randomly divided into four groups(12/group):(1)vehicle(VH)group:intraperitoneal injection of olive oil 1 ml/(kg·d)and normal saline 2 ml/(kg·d);(2)VH+PK group:intraperitoneal injection of olive oil 1 ml/(kg·d)and PK 7.2 U/(kg·d);(3)TAC group:intraperitoneal injection of TAC 1.5 mg/(kg·d)and normal saline 2 ml/(kg·d);(4)TAC+PK group:intraperitoneal injection of TAC 1.5 mg/(kg·d)and PK 7.2 U/(kg·d).After 4 weeks of the above treatment,the rats were sacrificed,and samples of blood,urine,and kidney tissues were collected.The general biochemical indicators and renal function were detected,and pathological observation was used to evaluate renal interstitial fibrosis.ELISA and Western blotting were used to detect the expression of inflammatory factors,fibrogenic factors,and antioxidants,and ELISA was also used to detect oxidative DNA markers.Results Compared with the VH group,the TAC group had higher levels of serum creatinine(Scr)and blood urea nitrogen(BUN),more renal interstitial fibrosis,more expression of transforming growth factor-β1(TGF-β1)and interleukin 6(IL-6),higher levels of serum and urine 8-hydroxydeoxyguanosine(8-OHdG),and more expression of ectodermal dysplasia-1(ED-1)and osteopontin(OPN)in cells(P<0.05),but showed lower level of manganese superoxide dismutase(MnSOD)(P<0.05).Compared with the TAC group,the TAC+PK group had lower levels of Scr and BUN,less renal interstitial fibrosis,less expression of TGF-β1 and IL-6,lower levels of serum and urine 8-OHdG,and less expression of ED-1 and OPN in cells(P<0.05),but showed higher level of MnSOD(P<0.05).Conclusion PK treatment alleviated the TAC-induced renal insufficiency,renal interstitial fibrosis,interstitial inflammation,and oxidative stress.PK treatment may have a protective effect on TAC-induced kidney damage.

关 键 词：他克莫司 胰激肽原酶 氧化应激 肾纤维化 

分 类 号：R73[医药卫生—肿瘤]