CAJ | 학술논문

目的观察不同时间输注骨髓间充质干细胞(MSC)对大鼠肾脏缺血再灌注损伤(IRI)的影响.方法以切除一侧肾脏夹闭对侧肾血管的方法制备肾IRI大鼠模型,3个实验组分别于恢复肾血流前2 h(灌前组)、恢复肾血流即刻(即刻组)和恢复肾血流6h时(灌后组)经尾静脉注射经荧光染料标记的MSC 2×106个,并设不输注MSC的对照组(IR组)和假手术对照组(假手术组).观察输注MSC后6h肾组织中MSC的分布情况；检测再灌注后6、24和48 h的血肌酐(Cr)和尿素氮(BUN)水平；观察再灌注后48 h的肾组织病理改变和肾小管上皮细胞凋亡情况.结果输注MSC者均可在肾脏中观察到MSC,以灌后组最多(P＜0.05).再灌注后24 h和48 h时,输注MSC者的血Cr和BUN与假手术组比较,差异均无统计学意义(P＞0.05),但均明显低于IR组(P＜0.05).与IR组比较,输注MSC者的肾脏病理损伤减轻,细胞凋亡数减少,以灌后组的改善最为明显(P＜0.05).结论输注MSC可减轻大鼠肾脏的IRI,这一效应在再灌注后输注MSC者最为明显,可能是通过减轻炎症反应和抑制肾小管细胞凋亡来减轻IRI.
목적 관찰불동시간수주골수간충질간세포(MSC)대대서신장결혈재관주손상(IRI)적영향.방법 이절제일측신장협폐대측신혈관적방법제비신IRI대서모형,3개실험조분별우회복신혈류전2 h(관전조)、회복신혈류즉각(즉각조)화회복신혈류6h시(관후조)경미정맥주사경형광염료표기적MSC 2×106개,병설불수주MSC적대조조(IR조)화가수술대조조(가수술조).관찰수주MSC후6h신조직중MSC적분포정황；검측재관주후6、24화48 h적혈기항(Cr)화뇨소담(BUN)수평；관찰재관주후48 h적신조직병리개변화신소관상피세포조망정황.결과 수주MSC자균가재신장중관찰도MSC,이관후조최다(P＜0.05).재관주후24 h화48 h시,수주MSC자적혈Cr화BUN여가수술조비교,차이균무통계학의의(P＞0.05),단균명현저우IR조(P＜0.05).여IR조비교,수주MSC자적신장병리손상감경,세포조망수감소,이관후조적개선최위명현(P＜0.05).결론수주MSC가감경대서신장적IRI,저일효응재재관주후수주MSC자최위명현,가능시통과감경염증반응화억제신소관세포조망래감경IRI.
Objective To observe the protection and distribution of bone marrow mesenchymal stem cells (MSCs) by distinct intravenous infusion time on renal ischemia reperfusion injury (IRI) in rats.Methods We used unilateral nephrectomy and contralateral vascular occlusion method to establish renal IRI model in rats.The experimental groups which received 2 × 106 MSCs infusion through the tail vein,were subsequently divided into 3 subgroups:2 h pre-reperfusion (PreOp,n =16),immediately after reperfusion (Op,n =16),6 h post-reperfusion (PostOp,n - 16).The control groups included sham operation group (n =16) and ischemia group (n =16).Chemotaxis of DAPI-labeled MSCs was detected 6 h after administration in the IR kidney.Renal function was detected at 6,24,and 48 h respectively after operation. Forty eight h after operation,the renal tissues were harvested to observe the pathological changes by HE staining and the tubular epithelial cell apoptosis via TUNEL assay.Results MSCs were found in the experimental groups after IR in the kidney,most in PostOp group.Twenty-four and 48 h after reperfusion,there was no significant difference in Cr and BUN between the experimental groups and sham operation group (P＞0.05),but the levels of Cr and BUN in the experimental groups were significantly lower than in the IR group (P＜ 0.05). As compared with IR group,the renal pathological injury was alleviated,the number of apoptotic cells was decreased in the experimental group,most significantly in PostOp group (P＜0.05).Conclusion MSCs can reduce the inflammatory response and inhibit renal tubular cell apoptosis in rat renal IRI.Post-reperfusion administration of MSCs leads to the best chemotaxis efficiency and protection.