摘要
目的:探讨高压氧对大鼠肾缺血再灌注损伤(IRI)的影响及其机制。方法:成年健康Wistar大鼠60只,随机分为4大组,正常对照组(n=6)、假手术组(n=18)、肾缺血再灌注组(IR组,n=18)和肾缺血再灌注+HBO治疗组(HBO治疗组,n=18)。后3组又按再灌注后1h、3h和5h各分为3个亚组,每个亚组大鼠6只。各组先切除右肾,取左肾研究。正常对照组切除右肾后立即切取左肾备用。假手术组不阻断左肾动脉,肾IR组和HBO治疗组则采用钳夹肾动脉法建立左肾缺血再灌注损伤模型。HBO治疗组:在肾缺血再灌注后0h、2h和4h时分别将大鼠置于动物实验用高压氧舱内治疗1h之后,治疗压力为2(Atmosphere absolute,ATA)(0.1MPa),舱内氧浓度在98%以上。各组分别于再灌注后1h、3h和5h时检测血中SCr、BUN、MDA和TNF-α的含量,并取左肾组织用于石蜡切片和HE染色、流式细胞术(Flow cytometry,FCM)行Amn-nexin V/PI双染法检测细胞凋亡以及电镜检查。结果:(1)在IR组,血中检测指标量显著高于同时点正常对照组和假手术组(P<0.05);在HBO治疗组,各指标在术后不同时点的含量均较IR组明显降低(P<0.05)。(2)FCM结果显示,HBO治疗组细胞凋亡也显著低于同期IR组(P<0.05)。(3)肾组织中细胞凋亡与血中BUN、SCr、MDA和TNF-α值呈显著正相关(P<0.05)。(4)肾组织病理和肾组织超微结构的变化在HBO治疗组的损伤也明显轻于其他组。结论:(1)肾缺血再灌注后,血中氧自由基和促炎症因子的大量产生可促进肾组织细胞凋亡,从而加重肾损伤。(2)肾缺血再灌注后,肾组织大量细胞凋亡是导致肾功能损害的重要原因。(3)HBO抑制氧自由基和促炎症因子的产生,抑制组织细胞凋亡是HBO在肾缺血再灌注损伤过程中发挥肾保护效应的重要机制。(4)早期HBO治疗对减轻肾缺血再灌注损伤进而保护肾功能更为有利。
OBJECTIVE To explore the effect and the mechanism of hyperbaric oxygenation （HBO） on renal ischemia-reperfusion injury （IRI）. METHODS 60 adult healthy Wistar rats were divided into 4 groups randomly： normal group （n = 18）, sham operation group （n = 18）, control group of renal IRI （n = 18）, HIND treated group of renal IRI （n = 18）. The rats in posterior three groups were divided into 3 subgroups according the time： 1 h after reperfusion,3 h after reperfusion,5 h after reperfusion. Each subset contained 6 rats. The right kidney of the rats in all groups was excised and the left kidney was observed. The left kidney of the rats in normal group was excised immediately when the right kidney was excised. The left renal artery was blocked in the control group of renal IRI and the HBO treated group of renal IRI while the left renal artery was not blocked in the sham operation group. In HBO treated group of renal IRI, the rats were put in hyperbaric chamber for 1 h at the time of ischemia/reperfusion,2 h after reperfusion,4 h after reperfusion where the pressure was 0. 1 MPa and the oxygen concentration was 98% and above. The contents of the BUN,SCr,MDA and TNF-α in blood serum in all groups were detected at 1 h,3 h,5 h after reperfusion. And the left kidney was used in paraffin section and HE stain,FCM, electron microscope and detection of ap- optosis which was double staining of Amnnexin V and PI. RESULTS 1. In control group of renal IRI,the levels of BUN,SCr, MDA and TNF-α in blood serum were significantly higher than those in normal group and sham operation group （P〈0. 05）, and those in control group of renal IRI were significantly higher than those in HBO treated group of renal IRI at the different phase（P〈0. 05）. 2. FCM detection revealed that there were few apoptosis in renal tissues in normal group and sham operation group while lots of apoptosis in control group of renal IRI. There were significant differences in the expression of apoptosis between control group of renal I
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2011年第8期649-654,共6页
Chinese Journal of Hospital Pharmacy
