The Effect Of Fuyuan Capsule On HIF Expression Of Rat Kidney With Sepsis

Systemic inflamatory response syndrome(SIRS) is characteristic of infection with severe sepsis,which can lead to Multiple organ dysfunction(MODS).The morbility and mortality of patient in the Intensive care unit(ICU) is increasd correspondingly. The pathophysiologic mechanism of pathogenesis in sepsis is complicated.Of the three major system Nerve-immune-endocrine is actived by stress,with inflamation cascade expansion followed by immunization paralyzed.Microcirculation dysfunction and coagulation / anticoagulation imbalance intensify tissue ischemia and hypoxia, increased tissue damage, internal environmental disorders, lowered immunity, so that the further spread of infection.The develop of many advance high-technology diagnosis and treatment is also difficult to save the lives of critically ill patients, making the treatment of sepsis ineffective. The Traditional Chinese Medicine has been proved to be good efficacy in mediation of serious incurable condition,early treatment can improve disease progression and prognosis significantly .Therefore, we have produced sepsis model, and should be treated with Traditional Chinese Medicine Fu Yuan capsule,to observe its effect on the inflammatory response.ObjectiveModel of sepsis is produced for therapy of Fu Yuan capsule and investigate the difference of hypoxia-inducible factor-1(HIF-1) mRNA levels and serum inflammatory mediators interleukin-6 (IL-6) levels in sepsie rat kidney in contrast to Sham and CLP group. Evaluate organ histology and function change, thus to explore Traditional Chinese Medicine for organ protection mechanisms.Material and Methods120 male SD rats were randomly divided into five groups, sham-operation group, model group, low-dose Fu Yuan capsule group and high-dose Fu Yuan capsule groups, xuebijing group,each including 3h, 6h, 12h, 24h four time points,6 per group.Model group marked by cecal ligation and puncture,Sham group was performed as CLP without ligation and puncture of the cecum.The two FuYuan capsule group were also given CLP operation after four days of successive intragastric administration. Rats in each group count of 24h mortality,at each time point. rats blood sample from cardiac extracts serum IL-6 was measured by enzyme linked immunosorbent assay (ELISA),and biochemical changes in renal function Blood urea nitrogen(BUN) were analyzed.Rat kidney tissue HIFmRNA levels were detected by Polymerase chain reaction( PCR) assay at each time point. The major organs (heart, liver, spleen, lung, kidney)histologic and morphological changes were observed by Hematoxylin and rosin(HE) staining method.Result1,The 24-hour-mortality of rat was null in Sham group.Rat in CLP group had the mortality of 46%(11/24).Mortality in Low-dose Fu Yuan capsule group and High-dose Fu Yuan capsule group was 38%(9/24) and 26%(6/24) respectively.Mortality of xuebijing group was21%(5/24). Compared with the sham-operated group, other groups at all time points IL-6 were at a higher level, the difference was statistically significant (P <0.01). Model group, IL-6 levels continued to increase over time,The low-dose Fu Yuan capsule group, at each time point IL-6 had no significant change compared with model group(P> 0.05), high-dose Fu Yuan capsule group in 6h,12h,24h time piont Compared with model group, IL-6 levels decreased significantly (P <0.05).2,Levels of HIF-1mRNA expression in model group,Fu Yuan Low/High dose group were dramaticly higher, the difference was statistically significant compared with sham group (P <0.05 or P <0.01);Levels of HIF-1mRNA expression was higher in High-dose Fu Yuan 3h group,the remaining time point were lower, the difference was statistically significant compared with model group(P <0.05 or P <0.01); low dose Fu Yuan group 24h time points compared with model group, the difference was statistically significant (P < 0.05).3,Model group,the Fu Yuan capsule high-and low-dose group of IL-6 levels increased gradually over time, compared with the sham operation group at all time points the differences were statistically significant (P <0.01);Each time point IL-6 levels in High-dose Fu Yuan capsule group were lower compared with model group,but until 6h the difference proved significant (P <0.05);The Low-dose Fu Yuan capsule group had no significant change compared with model group (P> 0.05) .4,Compared with the sham-operated group, HE staining showed severe pathological change in organs of model group.Engorgement,swelling,degeneration and necrosis were found in hepatocytes. Focal atelectasis,erthrocyte exdudation in pulmonary alveoli were observed; myocardium appeared focal hemorrhage, glomerular capillary congestion occurs,Hyperemia,necrosis and detachment were found in ileum mucosa.Renal tissue of Fu Yuan high-dose group had reduced pathological change compared with model group. Model group, low-dose Fu Yuan capsule group 12h, 24h after surgery BUN found increased compared with the sham operation group, the difference was statistically significant (P <0.01);Fu Yuan capsule high dose group 12h, 24h time points BUN lowered ,the difference was statistically significant compared with model group (P <0.05). Fu Yuan capsule high dose group 24h time points BUN changed,the difference was statistically significant compared with sham group(P <0.05).ConclusionHIFmRNA and IL-6 elavate consistenly during sepsis,this show HIF has some realationship with IL-6.Fuyuan capsule high dose group could reduce damage in kindy,with its mechanism to regulate HIF expression.To some extent the two fuyuan capsule group could decrease death rate.this has some effect for sepsis prevention and cure.and aline with the drug administration.