Study Of The Molecular Mechanism Of The Protective Effects Of PDS On The Cardiopulmonary Injury Of Endotoxic Shock In Rats

Endotoxic shock concomitant with gram-negative bacteria infections remains a high mortality clinically since it is still in lack of effectsive measures of prevention and therapy. Therefore it has become the focus subject nowadays worldwide for researchers to explore some effectsive measures for prevention and therapy. According to the series of study made in our research laboratory, it has been demonstrated that PDS (panaxadiol saponins) has the similar anti-shock effects as dexamethasone in the treatment of hemorrhagic shock through its effects to improve microcirculation and to resist peroxidatic injury to perform a protection of cells and organic functions. Although endotoxic shock is identified as the high-output and low-resistance type of shock different from the hemorrhagic shock, deficiency of microcirculation and ischemia-anoxia is the general mechanism in the development and progress of shock. Thus, it is speculated that PDS may have some protective effects on endotoxic shock. Based on the great achievements in the research of the molecular mechanism of endotoxic in recent years, we made the study in this paper to investigate the protective effects of PDS on the cardiopulmonary function by building up the LPS-induced endotoxic shock model in rats, and to reveal the molecular mechanism as well. The protective effects of PDS on cardiac structure and function of endotoxic shock in rats. A hundred wistar rats were divided into 5 groups: the LPS endotoxic shock model group (LPS group); dexamethasone administered group (DEX group); PDS low-dose group (PDSL group); PDS mid-dose group (PDSM group); PDS high-dose group (PDSH group), and each group was divided into 2 groups: killed at 120min and killed at 240min. LPS (5mg/kg) was sublingually administered intravenously to build up the model of endotoxic shock. When blood pressure fell to 2/3 of the baseline it was regarded as the start of shock. Meanwhile, MABP, LVSP etc were monitored dynamically through the RM6000 4-lead physiologic recording apparatus, while serum myocardial enzymes were determined, and myocardial morphology was observed as well. The results are as follows: (1). It is found by the dynamic observation that, rats in all groups entered into shock state at 5min, and MABP and LVSP etc had an compensatory restoration at 10min of shock. In LPS group, the above index fell progressively since 45min of shock until the models got close to death at 240min. however, those indexes remained steady and constant compensatory changes in various doses of PDS groups and DEX group until the rats were killed at 240min of shock.(2) With the myocardial pathology, the focally distributed myocardial fiber was found in a disorder state and some fiber was found broken. Focal hemorrhage and denaturalization, lymphocyte and monocyte infiltration can be seen; the amounts of opening capillary vessels among myocardial fiber decreased significantly; and capillary vessels expansion and congestion were found. The above signs in PDS groups and DEX group are much better than those in LPS group, and same were the opening capillary vessels, but fiber rupture and hemorrhage were found. (3). Result of the determination of Serum AST, CK and LDH: the serum myocardial enzymes in LPS group is the highest among groups. The activity of enzymes in various dose of PDS groups are significantly lower than that in LPS group and showed the protective effects of PDS on myocardial cell membrane. (4). Result of hema-rheology: the blood viscosity in DEX group and PDS groups are all significantly lower under various shear rates than that in LPS group. It suggested that PDS can decrease blood viscosity, significantly improve microcirculation and increase the blood supply, and finally perform a protective effects on myocardial cells and the structure and function of organs. The molecular mechanism of pulmonary injury caused by LPS-induced endotoxic shock and the protective effects of PDS. (1). The histological and pathological changes: pulmonary tissues getting solidi...