The Influences Of XUE BIJING On The Levels Of ET-1 And Cr In Mice With Endotoxemia

Objective: Acute renal failure (AFR) caused by endotoxemia is one part of multiple organ failure (MOF). Mortality of patient with endotoxin AFR is still over fifty percent in spite of a rapid progress in antibiotics and other therapeutic method in clinical practice. Therefore, it is very important to study the mechanism of endotoxemia and effective methods to protect renal fountion. Endotoxin can directly or indirectly damage and activate vascular endothelial cell, which leading to more endothelin (ET-1) production. It is known that the interaction of ET-1 with other inflammatory mediators play an important role in the advancement of endotoxemia. It causes obvious and persistent vasoconstriction and decrease blood flow of organ, which resulting to MOF. It had been conformed that ET-1 has more aggravative effection than the endothelium-derived relax factor (EDRF) when the balance of ET-1 and EDRF was destroyed, which was the main reason and mechanism of ARF. Therefore, downregulating the founction of ET-1 has become the focus in treating renal disfunction. It has reported that traditional Chinese medicine XUE BI JING injection can aliviate endotoxin and downregulate inflammatory mediators and improve minicirculation. In this study, we investigated the effection of XUE BI JING on the levels of ET-1 in plasma and serum creatinine (Cr) in mice with endotoxemia.MethodPart one: Thirty-six healthy KunMing mice (male, 40-45g) were randomly divided into three groups: the control group (n=12), the lipopolysaccharide (LPS) group (n=12), and the treatment group (n=12). The mice of the LPS group were received intraperitoneal injection with LPS (10mg/kg). After 30 min of the injection of LPS (10mg/kg), the mice of treated group were received intraperitoneal injection with XUE BI JING (15ml/mg) and then repeated once 30 min later. Equal volume of normal sodium (NS) was injected into mice of the control group. The levels of ET-1 in the plasma were determined with radio-immunity kit at 3h and 6h after the injection of LPS.Part two: Thirty healthy KunMing mice (male, 40-45g) were randomly divided into three groups: the control group (n=10), the lipopolysaccharide (LPS) group (n=10), and the treated group (n=10). The mice of the LPS group were received intraperitoneal injection with LPS (10mg/kg). After 30 min of the injection of LPS (10mg/kg), the mice of treated group were received intraperitoneal injection with XUE BI JING (15ml/mg) and then repeated once 30 min later. Equal volume of normal sodium (NS) was injected into mice of the control group. The levels of ET-1 in the plasma were determined with radio-immunity kit at 3h and 6h after the injection of LPS. Serum Creatinine (Cr) were determined at 6h after the injection of LPS. The histopathological changes of the kidny were examined with HE staining of specimen under light microscopy.Result1. The changes of ET-1 in groups: Compared to the control group, the levels of ET-1 in LPS group were higher at 3h after LPS injection (P<0.01) and still higher at 6h(P<0.01). Compared to the LPS group, the levels of ET-1 in the treatment group decreased at 3h after LPS injection (P<0.01) and it was still lower at 6h (P<0.01).2. The changes of Cr in groups: Compared to the control group, the levels of serum Cr in LPS group were higher significantly at 6h after LPS injection (P<0.01). Compared to the LPS group, the levels of Cr in the treatment group decreased significantly after 6h injection of LPS (P<0.01). No significant changes between the control group and the treatment group.3. The histopathological changes of the kidny in groups: Compared to the control group, at 6h after LPS injection, analosis could be found in renal glomerulus, and renal capsule were dilatation. The renal glomerulus cells were apomorphosis, and hemorrhage was found in renal interstitium with inflammatory cells infiltration. Compared to the LPS modle group, the injury of kidney in the treatment group was alleviated.Conclusion1. XUE BI JING could down regulate the levels of ET-1 in plasma in mice with endotoxemia, which resulting to increase blood flow of organs and protect vascular endothelial cells.2. XUE BI JING could down regulate the levels of serum Cr, which can reduce injury of kidney in mice with endotoxemia. The protective effects may be contributed to the decrease of ET-1.