高压氧和丹参酮ⅡA联合治疗大鼠肾缺血-再灌注损伤的疗效观察

Effect of combination treatment of hyperbaric oxygen and tanshinone ⅡA on renal ischemia-reperfusion injury in rats

目的探讨高压氧和丹参酮ⅡA联合治疗大鼠肾缺血-再灌注损伤(RIRI)的疗效。方法选取SD大鼠120只,分为RIRI组(A组)、高压氧治疗组(B组)、丹参酮ⅡA治疗组(C组)、高压氧和丹参酮ⅡA联合治疗组(D组)、正常组(E组)和假手术组(F组),各组均为20只。各组观察期间均通过尾静脉在不同时间点采血(术前1h,术后1、3、5、7、14、30、60、90d)观察肾功能(肌酐、尿素氮)变化情况,取肾脏标本行HE染色、免疫组织化学检测层连蛋白(LN)、转化生长因子β1(TGF-β1)的表达。观察各组大鼠的死亡情况,并行死因分析。结果 D组肾功能的肌酐、尿素氮在术后第1天升高,第1～3天达高峰,第5～14天回落到基线水平,继而又缓慢上升,与其余各组比较,差异有统计学意义(P<0.05)。D组中位生存时间为63d,低于其余各组(A组为72d),且差异有统计学意义(P<0.05);A组病死率为55.00%,D组病死率为60.00%,与E组病死率(10.00%)比较,差异有统计学意义(P<0.01)。RIRI(RR=7.170,P=0.010,95%CI:1.587～32.389)与高压氧和丹参酮ⅡA联合治疗(RR=8.735,P=0.005,95%CI 1.951～39.114)均是导致大鼠死亡的危险因素。D组大鼠肾脏组织纤维化明显。结论高压氧和丹参酮ⅡA联合治疗大鼠RIRI早期有效,但对比单纯高压氧治疗、丹参酮ⅡA治疗无明显优势,且增加了晚期治疗后大鼠的病死率。

Objective To investigate the therapeutic effects of combination treatment of hyperbaric oxygen and tanshinoneⅡ A on renal ischemia-reperfusion injury(RIRI)in rats.Methods 120 SD rats were randomly divided into the untreated group(group A),the hyperbaric oxygen treatment group(group B),the tanshinoneⅡ A treatment group(group C),the hyperbaric oxygen and tanshinoneⅡ A combination treatment group(group D),the normal group(group E)and the sham group(group F)after renal ischemia reperfusion with 20 rats in each group.During the observation period,blood samples were taken from the tail vein at different time points(1 hour before surgery,and 1,3,5,7,14,30,60,90 days after surgery)to observe the renal function(creatinine and urea).Kidneys were taken for HE staining,and immunohistochemistry was used to measure the expression of LN and TGF-β1.The survival and the cause were analyzed.Results The creatinine and urea of renal function in group D increased at the 1 st day,peaked within 3 d(from the first to the third day),fell back to the baseline level from the fifth to the fourteenth day,and then slowly increased.There was a statistically significant difference between it and other groups(P<0.05).The median survival time for group D was 63 days which was lower than the other groups(72 days for group A),and the difference was statistically significant(P<0.05).The mortality in group A was 55.00%,which in group D was 60.00%.Compared with group E,the mortality was 10.00%,and there was a statistically significant difference(P<0.01).RIRI(RR=7.170,P=0.010,95%CI:1.587-32.389)and hyperbaric oxygen/tanshinoneⅡ A combination(RR=8.735,P=0.005,95%CI:1.951-39.114)were risk factors for death in rats.Renal fibrosis shows obviously in group D.Conclusion Hyperbaric oxygen/tanshinone ⅡA combination treatment is effective in the early treatment of RIRI in rats,but there is no significant advantage compared with hyperbaric oxygen therapy or tanshinoneⅡA treatment separately.Also,it increases the mortality of ischemia-reperfusion.