Protective Effects Of Penehyclidine On Lung Injury Induced By Renal Ischemia Reperfusion In Rats

Objective: In order to observe the protective effect of penehyclidine on lung injury induced by renal ischemia reperfusion in rats, and to investigate the underlying mechanism, and to provide preclinical pharmacological basis for its new clinical application.Methods: 32 healthy male wistar rats which weighing 250～300g, were randomly divided into 4 groups (n=8/group): sham operation group (group S), ischemia-reperfusion group (group I/R), penehyclidine of small-dose (group M), penehyclidine of high-dose(group N). In the sham group , renal artery was only isolated without clamping.The I/R model was established by clamping renal artery for 1 hour and reperfusing for 3 hours, penehyclidine was muscle- injected (0.5㎎/㎏ body weight, IP) at 15 minutes before artery open in Group M, penehyclidine was muscle- injected (2㎎/㎏ body weight, IP) at 15 minutes before artery open in Group N, Lung tissue samples were collected after reperfusion 3 hours. The left lobus superior pulmonis were removed for the levels of IL-10; and the right lobus medius pulmonis for lung water content, and then lobus inferior pulmonis for Pathology of light microscope and the expression of TNF-α, more over, The right lobus superior pulmonis were removed for Pathology of transmission electron microscope.Results:1 Pathology of light microscopeGroup S: By microscopy, the interalveolar septum had no thickening. The structure of alveoli was normal and the alveolar space was clear with the filtration of few inflammatory cells.Group I/R: In the I/R group, the obiviously thickened inieralveolar septum, the infiltration of inflammatory cells and the leakage of erythrocyte could be found. Group M: The pathological changes of lung was lighter than group I/R, and the structure of pulmonary alveoli was much clearer than group I/R.Group N: The pathological changes of lung was more serious than group M2 Lung water contentCompared With the group S, the content of water in lung was increased significantly in group I/R ,M and N (P<0.05), Compared with the group I/R, the content of water was decreased significantly in group M and N(P<0.05), Compared with the group M, the content of water was decreased significantly in group N (P<0.05).3 The content of TNF-αin lung tissueCompared With the group S, the content of TNF-αin lung tissue was increased significantly in group I/R ,M and N (P<0.05); Compared With the group I/R , the content of TNF-αin lung tissue was lower significantly in group M and N (P<0.05);Compared with the group M, the content of TNF-αin lung tissue was lower in group N (P<0.05).4 The content of IL-10 in lung tissue homegenateCompared With the group S, the content of IL-10 in lung tissue was lower significantly in group I/R, M and N (P<0.05); Compared With the group I/R , the content of IL-10 in lung tissue was higher significantly in group M and N (P<0.05);Compared with the group M, the content of IL-10 was higher in group N (P<0.05).5 Pathology of transmission electron microscopeGroup S: There were microvillus and the lamellar body in the Group type II cell. The cell organelles, mitochondria of lung were normal, and the basement membrane of air-blood barrier was very clear.Group I/R: There were a large number of red blood cells in alveolar space. The lamellar body and microvillus of type II cell decreased significantly. A large number of collagen fibershyperplasiaed,pulmonary closure was existed onpartial lung.Group M: The basement membrane of air-blood barrier was integrated,but there was a little became thicker and more uneven;Type II cells was normal.Mitochondria had mild damaged.Group N: The pathological changes of lung was more serious than group M.Conclusion:1) This study demonstrated that renial I/R may result in sincerely lung damage. 2) The mechanisms of the effect are due to its ability of inhibiting the activation of TNF-αand increasing the activation of IL-10...