ABSTRACT
Objective To investigate the effect of penehychdine hydrochloride (PHCD)on acute lung injury induced by acute severe acute pancreatitis and the expression of hypoxia inducible factor-1α(HIF-1α)in rats.Methods Forty healthy adult male SD rats were used and randomly divided into 3 groups, group S of sham operation,group ALI of pancreatitis-associated acute lung injury (PALI)and group P of PALI with PHCD.Rats of group ALI and group P were the model established of acute lung injury associated with SAP by retrograde injection of 4% sodium taurocholate into biliopancreatic duct.Rats of group P of acute lung injury with SAP were immediately given PHCD after SAP.Rats of group S and group ALI were injected the same amount of 0.9% sodium chloride solution.After modeling,the rats were sacri-ficed at 12 h.The wet/dry weight ratio (W/D)of lung tissue was calculated.Pathological changes of pan-creatic and lung tissues were scored.HIF-1α,IL-1β,IL-6 of lung tissues and serum amylase were detected by ELISA.The expression of TLR4,NF-κB p65 in lung tissue was detected by Western blot.Results Ex-tensive infiltration of neutrophils,alveolar hemorrhage and necrosis and fat necrosis with pancreatic tissue were observed in group PALI and group P.Pancreatic tissue injury score was significantly higher than that of group S (P <0.01).However,there was no statistically significant difference between the level of serum amylase in group P and group ALI.The W/D ratio of lung tissue in rats of group ALI and group P was sig-nificantly higher than those in group S (P <0.05).Compared with those of group ALI,the lung tissue pathological changes of group P were significantly improved,and the lung W/D value was significantly lower than that of group ALI (P <0.05).Compared with group S,the expression of TLR4,NF-κB p65,HIF-1αin lung tissue of group ALI and group P was significantly higher (P <0.01),and the expression of TLR4, NF-κB p65,HIF-1α,IL-1βand IL-6 in group P was significantly lower than that in group ALI (P <0.05).Conclusion PHCD could not alleviate the damage of pancreatic tissue of SAP.It suppressed the expression of HIF-1α,IL-1βand IL-6 and reduced the acute lung injury induced by SAP in rats,which might be depen-ded on suppressing the expression of inflammatory factors,such as HIF-1α.
ABSTRACT
Objective To investigate the effect of a selective muscarinic receptor antagonist (penehyclidine hydrochloride) in three vessel occlusion model of acute global cerebral ischemia-reperfusion in rats.Method One hundred and forty-four male SD rats were randomly divided into four groups:sham operated group,vehicle treated group (saline 1 ml,i.p.),scopolamine treated group (0.01 mg/kg,i.p.) and penehyclidine hydrochloride treated group (0.01 mg/kg,i.p.) with drugs injected 40 minutes before ischemia respectively.The ischemic duration was 10 minutes.The animals were subjected to motor activity tests (open field activity test,beam-walking test and grip test) at 24 hours or on the 3rd and 7th day after reperfusion.HE staining,TUNEL staining and immunohistochemical reactions of bax and bel-2 were carried out at the time points of 2,12,24 hours,3 and 7 days after reperfusion.TTC staining was carried out in some rats for assessment of infarction volume on the 4th day after reperfusion.Results As compared with the vehicle treated group,both penehyclidine hydrochloride treatment and scopolamine treatment decreased the numbers of apeptotie neurons (P