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远程缺血预处理对猪肾移植模型炎症无影响。

No effect of remote ischaemic conditioning on inflammation in a porcine kidney transplantation model.

作者信息

Secher Niels, Soendergaard Peter, Ravlo Kristian, Soelling Christoffer, Granfeldt Asger, Wogensen Lise, Keller Anna K, Moeldrup Ulla, Ostraat Ernst O, Joergensen Troels M, Jespersen Bente, Toennesen Else

机构信息

Department of Anaesthesiology and Intensive Care Medicine, Aarhus University Hospital, Noerrebrogade 44, Aarhus C 8000, Denmark.

Department of Renal Medicine, Aarhus University Hospital, Brendstrupgaardsvej 100, Aarhus N 8200, Denmark.

出版信息

Transpl Immunol. 2014 Aug;31(2):98-104. doi: 10.1016/j.trim.2014.05.005. Epub 2014 Jun 4.

Abstract

MAIN PROBLEM

Delayed graft function after kidney transplantation is associated with decreased graft survival and increased patient mortality but the pathogenesis is poorly understood. Remote ischaemic conditioning (rIC) may prevent delayed graft function by an anti-inflammatory effect. In a porcine model of transplantation from adults to children, we investigated the inflammatory response in the transplanted kidney and the effect of rIC.

METHODS

Kidneys were recovered from brain dead donor pigs(63kg) and transplanted into two groups of recipient pigs(15kg) after 22h of cold ischaemia. Recipients were randomised to either: rIC (n=8) performed before the 10-h reperfusion period or no-rIC (n=8). Non-transplanted kidneys from eight brain dead pigs served as controls.

RESULTS

Compared to controls, transplantation increased the number of apoptotic cells, macrophages and neutrophils in the kidney. After transplantation, IL-10 levels increased and IL-6 levels decreased in the kidney, whereas levels of TNF-α and IL-8 were not affected. A significant rise in plasma IL-1β and IL-6 was observed in the recipients after transplantation. Plasma IL-10 was not affected by transplantation and TNF-α and IL-8 were below detection limit. No effect of rIC was found with regards to cell infiltration or cytokine production.

CONCLUSION

Renal transplantation elicits an inflammatory response in the kidney manifested as apoptotic cell death, macrophage and neutrophil infiltration, and an anti-inflammatory cytokine response 10h after transplantation. This response was not modified by rIC.

摘要

主要问题

肾移植后的移植肾功能延迟与移植肾存活率降低及患者死亡率增加相关,但发病机制尚不清楚。远程缺血预处理(rIC)可能通过抗炎作用预防移植肾功能延迟。在一个从成年猪到幼年猪的移植模型中,我们研究了移植肾中的炎症反应以及rIC的作用。

方法

从脑死亡供体猪(63千克)获取肾脏,在冷缺血22小时后移植到两组受体猪(15千克)体内。受体被随机分为两组:在10小时再灌注期之前进行rIC的组(n = 8)或未进行rIC的组(n = 8)。来自八只脑死亡猪的未移植肾脏作为对照。

结果

与对照组相比,移植增加了肾脏中凋亡细胞、巨噬细胞和中性粒细胞的数量。移植后,肾脏中IL - 10水平升高,IL - 6水平降低,而TNF - α和IL - 8水平未受影响。移植后受体血浆中IL - 1β和IL - 6显著升高。血浆IL - 10不受移植影响,TNF - α和IL - 8低于检测限。未发现rIC对细胞浸润或细胞因子产生有影响。

结论

肾移植引发肾脏的炎症反应,表现为凋亡细胞死亡、巨噬细胞和中性粒细胞浸润以及移植后10小时的抗炎细胞因子反应。这种反应未被rIC改变。

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