Protection Of Penehyclidine Hydrochloridein Rat Lung With Hemorrhagic Shock-induced Acute Lung Injury

PART ONE EFFECTS OF PENEHYCLIDINE HYDROCHLORIDE PRETREATMENT ON ACTIVATION OF NF-ΚB IN LUNG TISSUE IN RATS WITH HEMORRHAGIC SHOCK INDUCED ACUTE LUNG INJURYObjective: To investigate the effects of penehyclidine hydrochloride(PHC) pretreatment on activation of NF-κB in rats with hemorrhagic shock induced Acute Lung Injury(ALI).Methods: Twenty-four normal Wistar rats of both sexes weighing 200-250g were randomly divided into 3 groups(n=8 each): groupⅠsham operation(S); groupⅡALI (A); groupⅢPHC (P). The animals were anesthetized with chloral hydrate 350 mg/kg. The ALI models were prepared in group A and P.Right internal carotid artery was cannulated for MAP monitoring.Left femoral artery was cannulated for bloodletting. MAP was reduced to 35-45mmHg within 10 min and maintained for 1 hour. Then the animals were resuscitated with blood transfusion and infusion of normal saline. In group P, PHC 2 mg/kg was given mainline instantly before bloodletting. The plasma was collected for determination of TNF-αcontent ( by ELISA). The lungs were harvested for determination of the expression of NF-κBp65 ( by immuno-histochemistry ) and lung W/D. Pathologic change in lung tissue were observed by light microscope.Results: Compared with group S, the lung tissue of group A dispiayed obvious pathologic change,plasma concentration of TNF-αincreased obviously(P<0.01), expression of NF-κBp65 in lung tissue increased obviously(P<0.01). Expression levels of NF-κBp65 and TNF-αwere significantly lower in group P than in group A(P<0.05).Conclusion: PHCD can attenuate hemorrhagic shock induced ALI by inhibiting the activation of NF-κB. PART TWO EFFECTS OF PENEHYCLIDINE HYDROCHLORIDE ON EXPRESSION OF CD40,CD40L IN LUNG TISSUE IN RATS WITH HEMORRHAGIC SHOCK INDUCED ACUTE LUNG INJURYObjective: To investigate the effects of penehyclidine hydrochloride(PHC) on expression of CD40,CD40L in rats with hemorrhagic shock induced Acute Lung Injury(ALI)and the effects of prognosis administration at different time points.Methods: Forty normal Wistar rats of both sexes weighing 200-250g were randomly divided into 5 groups(n=8 each): groupⅠsham operation (S); groupⅡALI (A); PHC treatment group 1, 2, 3 (goup P1, P2, P3, n=8), In group P1, PHC 2 mg/kg was given mainline instantly before bloodletting. In group P2, PHC 2 mg/kg was given mainline instantly after bloodletting. In group P3, PHC 2 mg/kg was given mainline instantly before reperfusion.Except the rats in groupⅠ, rest rats were made into hemorrhagic shock models with lung injury.Expression of CD40 and CD40L in lung tissue were measured by immunohistohemistry. The plasma concentration of TNF-αand IL-10were measured by ELISA. Pathologic change in lung tissue were observed by light microscope.Results: Compared with group S, the lung tissue of group A dispiayed obvious pathologic change,plasma concentration of TNF-αand IL-10 increased obviously(P<0.05), expression of CD40 and CD40L in lung tissue increased obviously(P<0.05). Expression levels of CD40, CD40L, TNF-α, IL-10 were significantly lower in group P1, P2, P3 than in group A(P<0.05). Expression levels of CD40, CD40L, TNF-α, IL-10 were significantly lower in group P1, P2 than in group P3(P<0.05) .Conclusion: PHCD can attenuate hemorrhagic shock induced lung injury by inhibiting the expression of CD40, CD40L. Given early Penehyclidine significantly improved the prognosis.