Effect and mechanism of Shenfu injection on vascular endothelial injury in septic rats
Objective It is to investigate the protective effect of early application of Shenfu injection on vascular endo-thelial injury in rats with sepsis,and to explore its possible mechanism.Methods Forty-eight male SD rats were randomly divided into sham operation group,sepsis group and Shenfu injection group,with 16 rats in each group.The rats of the sepsis group and Shenfu injection group were prepared by cecum ligation and perforation to establish models of sepsis,while the rats of the sham operation group only underwent laparotomy to expose the cecal.Starting from 1 h after cecal ligation puncture,the Shenfu injection group was injected intraperitoneally with Shenfu injection(6 mL/kg)every 12 h,and the remaining two groups were injected with equal quality normal saline at the same time.The behavioral performance of rats in each group was observed in 48 h after surgery,and the survival rate of rats was counted;the surviving rats in each group were executed in 48 h after surgery,and the histopathological morphology of aortic tissue was observed by HE staining,the serum levels of tumor necrosis factor-α(TNF-α),interleukin-10(IL-10),tissue factor(TF),thrombomodulin(TM),von Willebrand factor(vWF),and fibrinogen activator inhibitor-1(PAI-1)were determined by ELISA,and the expres-sions of inhibitory subunit of NF-κBα(IκBα),nuclear factor-κB(NF-κB)p65 protein and their respective phosphoryla-tion in aortic tissues were detected by Western blot.Results Poor hair,sluggish response to the outside world,diarrhea,blood oozing from the nose and eyes,congestion,edema and necrosis of the intestinal mucosa were found in the rats of the sepsis group,and light microscopy showed that there were hyperplasia,swelling and detachment of the aorta endothelial cells with rupture of the inner elastic membrane.Compared with the sepsis group,the mental and hair status,activity,di-arrhea,blood oozing from the nose and eyes,intestinal edema and necrosis,and pathological changes of the aorta under light microscopy of the rats of the Shenfu injection group were significantly improved.At 48h after operation,the survival rate of rats in the Shenfu injection group was significantly higher than that in the sepsis group(P＜0.05).The levels of TNF-α,IL-10,TF,TM,vWF,PAI-1 in peripheral blood and the relative expressions of p-IKBα and p-NF-κB p65 pro-teins in aortic tissues of rats of the sepsis group were significantly higher than those in rats of the sham operation group(all P＜0.05),and the levels of TNF-α,IL-10,TF,TM,vWF,PAI-1 in peripheral blood and the relative expressions of p-IKBα and p-NF-κB p65 proteins in aortic tissue of rats of the Shenfu injection group were significantly lower than those in rats of the sepsis group(all P＜0.05).Conclusion Early application of Shenfu injection can inhibit the body inflammatory response,reduce vascular endothelial injury in rats with sepsis,and have a certain protective effect on coagulation dysfunc-tion caused by sepsis,the mechanism may be related to inhibiting the activation of IKBα/NF-κB signaling pathway.
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