Therapeutic Effects Of Penehyclidine Hydrochloride On Septic Rats

Objective: To establish the septic animal model with cecal ligation and puncture(CLP), and to evaluate the therapeutic effects of Penehyclidine Hydrochloride on septic rats.Methods:Thirty-six male Wistar rats weighing 250-300g were used in this study .The animal were randomly divided into 3 groups (n=12): (S) sham group; (CLP) cecal ligation and puncture group; (PHC) Penehyclidine Hydrochloride group. (1) S group: the rats′abdomen only be opened.(2) CLP group: the rats′abdomen was opened, then the caecum was ligated and punctured. (3) PHC group: treated with Penehyclidine Hydrochloride of 2mg/kg through intrapertoneal injection after CLP. After operating, saline 3⁴ml/100g was injected subcutaneously. Collect blood sample from carotid artery at 0h and 12h. The PaCO₂, PaO₂, Lac and pH were recorded. Data were expressed as mean±SD. Statistical analysis was performed using SPSS 11.5 software Package. P<0.05 was considered significant for all statistical analyses. We observed the general status After 12 h, the cardiac, lung, hepatic , renal histopathology changes were observed with light microscopy and transmission electron microscopy technique. Results:1 There are no difference of the rats′weight among the three groups. At 0 h, there are no difference of PaCO₂, PaO₂ , Lactate(Lac) and PH among the three groups.2 The general status of rats: the rats in the Sham group recovered earlier than that in other groups and act as normal. No abdominal dropsy and evil smelling were found when their abdomens were opened. The rats in CLP group recovered later than that in the Sham group, and then were depressed with inaction, piloerection, and tachypnea. When the abdomen was opened, bloody ascites and evil smelling were found and bowels looked edema. The cecum was darkened in some rats. Compared with the CLP group, the clinical manifestations in the rats of PHC group were better.3 PaCO₂: The PaCO₂ value in the CLP group was significantly increased compared with that in the S group at 12 h point. (12h: 61±5.7mmHg vs 43±4.0mmHg);The PaCO₂ value in the PHC group was significantly decreased compared with that in the CLP group at 12 h point. (12h: 52±4.4mmHg vs 61±5.7 mmHg) 4 The PaO₂: The Pao2 value in the CLP group was significantly decreased compared with that in the S group at 12 h point. (12h: 87±5.5mmHg vs 103±6.0 mmHg);The PaO₂ value in the PHC group was significantly increased compared with that in the CLP group at 12 h point. (12h: 97±4.0mmHg vs 87±5.5mmHg). 5 The pH:The pH value in the CLP group was significantly decreased compared with that in the S group at 12 h point. (12h: 7.20±0.09 vs 7.37±0.03);The pH value in the PHC group was significantly increased compared with that in the CLP group at 12 h point (7.29±0.04 vs 7.20±0.09).6 The Lac: The Lac level in the CLP group was significantly increased compared with that in the S group at 12 h point. (12h: 4.5±0.8mmol/L vs 2.0±0.5mmol/L);The Lac level in the PHC group was significantly decreased compared with that in the CLP group at 12 h point (12h:3.2±0.5mmol/L vs 4.5±0.8mmol/L).7 The results of light microscopy:In the S group , the structure of myocardial fibers, lung tissue, hepatic cells and renal tubules were normal; In the CLP group, myocardial fibers were edema and curmbly, myocardial fiber mesenchymal was congestive and edema. The lung tissue was heavy and alveolar septum was wide. The hepatic cells were edema, sinus hepatics and portal tract were congestive. Renal tubule were dilated and congestive, interstitial vascular were dilated and congestive. Renal tubular epithelial cells were edema and the lumens were narrow, some renal tubular epithelial were vacuolar or hyaline degeneration. In the PHC group, the histopathology changes in PHC group were not as serious as that in CLP group.8 The results of transmission electron microscopy: In the S group, the structure of myocardial fibers, lung tissue, and hepatic cells were normal; In the CLP group, the injury was seriously. In the PHC group, the injury was ameliorated effectively. Conclusion : Penehyclidine Hydrochloride has partial therapeutic effects on septic rats.