Protective Effects Of Penehyclidine Hydrochloride Against Acute Lung Injury Induced By Sepsis In Rats

Objective: Sepsis is defined as suspected or proven infection plus a systemic inflammatory response syndrome. Acute lung injury (ALI) is one of the common complication of sepsis. ALI / ARDS are the performance of SIRS at lungs, they are not isolated partition of the disease, but different stages of serious injury caused by SIRS. In this study, ALI was induced by the operation of cecal ligation and puncture (CLP). After observing the expressions of relative inflammatory mediators and the alterations of pathology in lung tissues, we explore the protective effects of penehyclidine hydrochloride against Acute Lung Injury induced by Sepsis.Methods: The septic rat model was established by cecal ligation and puncture. 36 healthy male Wistar rats were randomly divided into 3 groups (n=12):①Sham group: open abdomen, expose cecum but without CLP.②CLP group: perform CLP.③PHC group: after CLP, intraperitoneal inject PHC 2mg/kg, Sham group and CLP group, intraperitoneal inject the same volume saline, then subcutaneous injection saline (30~40mg/kg) in each group to prevent shock. Observe the general status of rats. After 12 hours, the rats were sacrificed and the tissue samples including lung and blood samples were collected. PaO2, PaCO2 .and pH were measured. The levels of TNF-αand IL-6 in serum were detected by radio immunity. Pathological changes of lung tissues were observed by light and transmission electron microscopy. Wet weight was measured immediately and dry weight was measured after drying specimens at 80°C for 48 hours to constant weight. The lung wet/dry weight ratio was then calculatedResults:1 The general status observation: The rats of CLP group had series of symptoms such as rarely exercise, refusal of drink, piloerection and tachypnea. When the abdomen was opened-closed , bloody ascites and evil smelling were found, the bowels looked edema. The rats of Sham group analepsied ealier and act as normal. While in the PHC group, the symptoms of majority rats were much mild than that of the rats in CLP group2 Changes of blood gas analysis: Compared with the Sham group, PaO2, pH in the CLP group were significantly decreased (P< 0.05), PaCO2 were significantly increased (P< 0.05); Compared with the CLP group, PaO2, pH in PHC group were significantly increased (P<0.05), PaCO2 were significantly decreased (P<0.05)3 The light microscopy results showed that in Sham group, the structure of alveoli and interalveolar septum was normal, the alveolar space was clear with the filtration of few inflammatory cells. In the CLP group, the obviously thickened interalveolar septum, pulmonary edema, inflitration of inflammatory cells and the leakage of erythrocyte could be found. Compared with CLP group, the pathological changes in PHC group were much mild.4 The transmission electron microscopy results showed that: Pulmonary microvascular basement and typeⅡpneumocyte in Sham group were maintained with normal. At the same time, Pulmonary microvascular basement membrane was not integral, most microvilli disappeared and lamellar body was evacuated in the CLP group. In the PHC group, these pathological changes were significantly attenuated.5 The alterations of W/D weight ratio of lung tissues: Compared with the Sham group, the W/D weight ratio of lung tissues in the CLP group increased significantly (5.4064±0.2353 vs 4.3976±0.2037, P<0.05);the W/D weight ratio of lung tissues in the PHC group increased significantly (4.7162±0.2356 vs 4.3976±0.2037, P< 0.05). Compared with CLP group, the W/D weight ratio of lung tissues in the PHC group decresed (4.7162±0.2356 vs 5.4064±0.2353, P<0.05)6 The levels of TNF-αand IL-6 in serum. The levels of TNF-αin serum of Sham group rats are lower than those of CLP group and PHC group, and the differences are significantly (0.8352±0.044 vs 1.6699±0.0630, P<0.01; 0.8352±0.044 vs 1.2574±0.0683, P<0.01); The levels of TNF-αin serum of PHC group was decreased compared with CLP group (1.2574±0.0683 vs 1.6699±0.0630 ,P <0.01); The levels of IL-6 in serum of Sham group rats are lower than those of CLP group and PHC group, and the differences are significantly (116.2510±6.7318 vs 156.1840±8.7588, P<0.01; 116.2510±6.7318 vs 119.500±11.4559, P<0.01);The levels of IL-6 in serum of PHC group was decreased compared with CLP group (119.500±11.4559 vs 156.1840±8.7588, P <0.01).Conclusions:1 The model of sepsis in rats could be established by cecal ligation and puncture (CLP) successfully.2 Penehyclidine hydrochloride inhibit the levels of TNF-αand IL-6 in serum thus provided protective effects against acute lung injury induced by sepsis.