| Sepsis is a systemic inflammatory response syndrome caused by infection.According to the Centers for Disease Control and Prevention,there were more than 2 million 400 thousand deaths from sepsis from 1999 to 2014,accounting for 6% of the total death toll.Sepsis is not only a severe clinical disease but is also defined as an event that impairs public health and safety.There are many pathogenic factors in sepsis.The pathogenesis of this disease is related to inflammation,disturbance of immunity,coagulation abnormality,and tissue damage.It is closely related to the pathophysiological changes of many systems and organs in the body.Studies show that most patients with sepsis die from multiple organ dysfunctions,while the kidney is one of the most sensitive organs of sepsis,and 42% of sepsis patients have acute kidney damage.Therefore,the treatment of acute kidney injury in sepsis plays a significant role in reducing the mortality of sepsis.So far,inflammatory response plays a key role in the development and progression of acute kidney injury in sepsis.Inflammation is a defense mechanism of the organism.The sequential synthesis and release of inflammatory mediators are the core driving force for the development of inflammation.Nuclear transcription factor kappa B(NF-KB)is an essential regulator of inflammation related genes transcription factor activation can induce various inflammatory transcription factor.Under physiological conditions,a majority of NFkappa B two polymer in cells is inactive in the cytoplasm,the anchor protein and inhibitor I kappa B is bound.When the body was immune stimulation,activation of the I kinase complex IKK kappa beta phosphorylation,expose nuclear localization,free p65 quickly shift to the nucleus,in combination with the particular speed of kappa B sequence leads to transcription of genes involved in inflammation.It reported that NF-?B of sepsis induced acute kidney injury activation.Resveratrol is a polyphenolic compound widely found in plants,especially in grapes,Polygonum cuspidatum and peanuts.Resveratrol not only has an inhibitory effect on acute inflammation but also has the same effect on chronic inflammation.However,the anti-inflammatory mechanism is not entirely understood.Whether resveratrol can protect the acute kidney injury of sepsis by regulating the NF-?B/I?B pathway has not yet been reported.In this study,pathological changes of NF-?B/I?B in the kidney of septic rats observed by pathological HE staining,renal function,and Western blot.2Cecal ligation and puncture model(CLP)used in this study.60 male SD rats at 13~15 weeks,weighing 200 to 250 g,SPF class.60 rats were randomly divided into 6 groups(n=10),sham,0h,6h,12 h,18h,and 24 h,respectively.According to the standard operating procedure of cecal ligation and puncture,the model was made.Then observe the model rats after 24 hours of activity,there is a vital sign,laparotomy,biopsy,renal function,expression of inflammation related proteins to judge the success of modeling and drug intervention suitable time point.The experimental drug intervention,13 ~ 15 weeks of 30 male SD rats weighing 200 ~ 250 g,SPF Were randomly divided into 3 groups,sham operation group(n=10): simple laparotomy without ligation puncture,then the abdomen was closed;sepsis group(n=10): application of cecal ligation and puncture method open service after the establishment of animal models for sepsis;resveratrol group(n=10): preoperative intraperitoneal injection for 5 days resveratrol,a daily dosage of 15mg/kg,then open by cecal ligation and puncture method to establish the model of sepsis.Three groups of rats received isoflurane induction and maintenance at 18 hours after the operation.Abdominal aorta was taken for detecting renal function.The left kidney was used for pathological examination,and some kidney tissues were taken for Western blot.The activity of the rats within 24 hours after modeling have observed a vital signs,laparotomy,biopsy,renal function,inflammation related protein expression and survival rate in 18 hours,model rats significantly reduced activity,unstable vital signs,laparotomy found necrosis and cecum.The ascites,further pathological examination showed that the renal tubular expansion,renal tubular epithelial cell shedding,and tube formation.At the same time,the expression of TLR4 also increased significantly.Drug intervention experiment results show that sham operation group(group Sham)glomerular and renal tubular structure is normal,no obvious interstitial edema In the sepsis model group(group Clp),the renal tubular dilatation was obvious,and some renal tubular epithelial cells became degeneration,necrosis,and desquamation,and many tubular types were formed.In the sepsis model group(Clp+Res group)pretreated with resveratrol,kidney damage was reduced,renal tubular dilation decreased,and tubular type decreased.The BUN and Cr values in group Clp were significantly higher than those in group Sham(P<0.05).Compared with group Clp+Res,BUN and Cr of group Clp+Res were significantly lower than those in group Clp(P<0.05).Compared with group Sham,the expression of the Pp65 protein in Clp group increased significantly,with statistical difference(P<0.05).The expression of Clp+Res in group Pp65 was considerably lower than that in group Clp(P<0.05).The expression of IKK-beta protein in Clp group was significantly higher than that in group Sham(P<0.05),and the expression of IKK-beta in Clp+Res group was significantly lower than that in group Clp(P<0.05).The expression of I kappa B protein in group Clp was significantly lower than that in group Sham(P<0.05),and the expression of I kappa B in group Clp+Res was significantly higher than that in group Clp(P<0.05).This study has preliminarily confirmed that resveratrol can alleviate acute kidney injury in sepsis and may be related to inhibiting the inflammatory pathway of IKK-I kappa B-Pp65 and reducing the inflammatory response of the renal tissue. |
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