The Effect Of Penehyclidine Hydrochorride On The Lung Injury After Ischemia-Reperfusion Of Limbs In Rats

Background and Objective:Ischemia-Reperfusion of slimbs usually happen on abdominal aortic aneurysm surgery , re-canalization of great vessels'embolism and injury recovery , replantation of severed limb , extracorporeal circu-lation etc. The large scope of ischemia may induce not only Ischemia—Reperfusion of slimbs, but also theinjury of further organ ( as lung) even multiple organ failure .With regard to the mechanism of acute lung injury following Ischemia--Reperfusion of slimbs , most scholars consider that chain reaction of generous oxygen-derived free radicals produced from Ischemia--Reperfusion of slimbs, activation of generous neutrophilic granulocyte, the production of mediators of inflammation and increased of proteolytic enzyme are the center links of inducing lung injury .Someone also discoveried that anticholine drugs had cytoprotection , can boost the cell' tolerance of ischemia and hypoxia, stabilize subcellular structureof cytolysosome and cytochondriome, decrease the releasing of cytreleasing, inhibit forming metabolite of arachi-donicacid and shock factor. All of those profit to relief small blood vessel spasm, dilate Ve-ssel , reduce the before and behind load of heart and the lung water after injury of lung. Penehyclidine Hydrochorride has obviously protection to the patient after intracardiac operation under direct vision and extracorporeal circulation.The purpose of this topic is to approach the mechanism of the effect of Penehyclidine Hydrochoride on the Lung Injury after Ischemia--Reperfusion of Limbs in rats through observing the structures of lung'patho-changing under electron microscope , determining and computering the water ratioes of lungs , detecting the content of TNF-a and IL-10 in lung' homogenate , and provide the evidence to clinical research.Materials and Methods:(1)Preparing the rat models of .Ischemia-Reperfusion Rats were labeled, grouped and anesthetized by injecting in abdominal cavity with 4% chloral hydrate , separated femoral artery and femoral vein , then occlusioned the femoral artery to cause to ischemia slims. (2) Medication Group I (control group ) and groupII ( injury group ) weren't aderministered , group III was given Penehyclidine Hydrochoride according to the dose of 2mg/kg , group IV was given 9mg/kg.(3) Observation index structures of lung' patho-changing under electron microscope , water ratioes of lungs , contents of TNF-a and IL-10 in lung'homogenate. (4)The data were expressed as mean±SD. Statistical package (SPSS 10.0) was used for processing data. P<0.05 was considered statistically significant.Result(1). General rat data : There were no significant differences among four groups in age. weight, the time of anesthesia > operation and Ischemia--Reperfusion (P > 0.05).(2). Water ratio of lung : The water ratio of group II was obviously higher than group I (P < 0.05). The water ratio of group IV was obviously fewer than group II andIII (P< 0.05).(3).Electron microscope observation : Lung capillary basement membranes of group I were comparatively complete , type II penumonocytes were round or ellipse , had plentiful endochylema , microvilli and laminated bodies were comparatively complete , the continuities of group II and group III were abscised, the cells of capillary endothelium were swelling, endothelial cells'intercellular space were widen, type II penumonocyte microvilli were seriously destroyed and became shorter , fewer, even disappeared. Type II penumonocyte laminated body were empty. The microstructure of group IV was only lightly destroyed, degree of injury was between group I and group II.(4). The content of TNF-a and IL-10 in lung tissue homogenate: The content of TNF-a in group II was obviously higher than group I (P < 0.05). The content of IL-10 in group II was obviously fewer than group I (P < 0.05). The content of TNF-a in group IV was obviously fewer than group II and III(P < 0.05). The content of IL-10 in group IV was obviously higher than group II and lll(P < 0.05).Conclusions:(1) Ischemia—Reperfusion of slimbs can cause to injury of further organs(as lung) , even multiple organ failure.(2) This experiment confirmed that proinflammatory cytokines TNF-a is the key cytokines which induce ALI correlated with Ischemia—Reperfusion of slimbs . The plasma level of IL-10 educe strong anti-inflammatory function.(3) Large dose of Penehyclidine Hydrochoride can utility restrain mediators of inflammation reliese alveolar exudation and protect capillary basement membrane, profit to relief small blood vessel spasm , dilate vessel , reduce the lung water after injury of lung.