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Effect Of Inuslin Intensive Therapy On The Serum Tnf-α Levels And The Expression Of Nf-κb In The Livers Of Diabetic Critically Ill Rats

Posted on:2006-03-06Degree:MasterType:Thesis
Country:ChinaCandidate:X L ZhangFull Text:PDF
GTID:2194330332470213Subject:Geriatrics
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Objective Recent studies have proved that the chance of diabetic patients occur critically ill condition and need surgery was more than non-diabetic patients.While in the treatment of diabetic critically ill patients,we have found insulin intensive therapy can increase the chance of survival and reduce mortality. Nuclear factor-kappaB(NF-κB) is a nuclear factor,which connect point of regulate translation is situated in the promoters of many pro-inflammatory cytokines gene and immunity regulation factors gene. NF-κB plays a important role in inducing the inflammation of critical illness. Tumor necrosis factor-α(TNF-α) is a cytokine which secreted by activated monocyte and macrophage. Recent studies have proved that TNF-αplays a important role in the cellular information transmission,infection and inflammation after trauma. The study aims at investigating the effect of insulin intensive therapy on NF-κB expression in the liver and the levels of serum TNF-αand IL-6 in diabetic critically ill rats,and observe the mortality of insulin intensive therapy group and insulin conventional therapy group.It provided theory basis for treating the diabetic critically ill patients.Methods 60 male Wistar rats were received intraperitoneal injection of 0.1% streptozotocin(55mg/kg) to establish diabetic models.30 diabetic rats were made into 30% TBS deepⅡdegree scald models.Then they were randomized into 2 groups:scald intensive therapy group(n=15) and scald conventional therapy group(n=15). Other 30 diabetic rats were made into the trauma models. Rats with closed injury with fracture in both hind limbs were adopted as the trauma models.Then they were randomized into 2 groups:trauma intensive therapy group(n=15) and trauma conventional therapy group(n=15).Blood glucose was maintained at the level of 3.9-5.6mmol/L in the intensive therapy group,and 10-12mmol/L in the conventional group.Blood was collected at 24h,4d,10d,and the levels of TNF-a and IL-6 were examined through ELISA.At the 10th day,the livers were collected,then the expression of NF-κB was observed by immunohistochemistry. Statistical treatment drew assistance from SPSS11.5.Results 1. The results of immunohistochemistry:①There were little stramineous granulo-substance expression in the cytoplasm and nucleus of hepatocytes through high power lens in the scald intensive therapy group and the trauma intensive therapy group.②There were many brown granulo-substance expression in the cytoplasm and nucleus of hepatocytes through high power lens in the scald conventional therapy group and the trauma conventional therapy group.③Through counting scores,it exhibited that the expression of NF-κB in scald intensive therapy group was significantly lower than that in scald conventional group(P<0.01),and the expression of NF-κB in trauma intensive therapy group was significantly lower than that in trauma conventional group(P<0.05).2.The serum levels of TNF-a:①The serum levels of TNF-a in the diabetic scald group:in the scald intensive therapy group the serum levels of TNF-a at 24th hour,4th day and 10th day after scald were (210.0±25.4)pg/ml,(147.9±10.5)pg/ml and (130.3±37.8)pg/ml respectively. In the scald intensive therapy group the serum levels of TNF-a at 24th hour,4th day and 10th day after scald were (423.9±72.0)pg/ml,(362.5±99.9)pg/ml and (289.6±120.2)pg/ml respectively. We can find that the serum levels of TNF-a in both groups take on decline tendency,and the peak is at the 24th hour. The serum levels of TNF-a in the intensive group were significantly lower than those of the conventional group (P<0.01).②The serum levels of TNF-a in the diabetic trauma group:in the trauma intensive therapy group the serum levels of TNF-a at 24th hour,4th day and 10th day after scald were (210.0±25.4)pg/ml,(147.9±10.5)pg/ml and (130.3±37.8)pg/ml respectively. In the trauma intensive therapy group the serum levels of TNF-a at 24th hour,4th day and 10th day after scald were (366.5±66.5)pg/ml,(324.9±114.7)pg/ml and (288.2±158.6)pg/ml respectively.We can find that the serum levels of TNF-a in both groups take on decline tendency,and the peak is at the 24th hour. The serum levels of TNF-a in the intensive group were significantly lower than those of the conventional group (P<0.01).④Comparison between the sclad intensive therapy group and the trauma intensive therapy group:In the scald intensive therapy group the serum levels of TNF-a at the 24th hour and the 10th day had no significant difference with the serum levels of TNF-a in the trauma intensive therapy group (P>0.05). The serum levels of TNF-a in the scald intensive therapy group at the 4th day had significant difference with the serum levels of TNF-a in the trauma intensive therapy group (P<0.05).④Comparison between the sclad conventional therapy group and the trauma conventional therapy group:In the scald conventional therapy group the serum levels of TNF-a at the 24th hour,the 4th day and the 10th day had no significant difference with the serum levels of TNF-a in the trauma conventinal therapy group (P>0.05).3.Comparision of mortality:①The mortality of the scald intensive therapy group was significant lower than the scald conventional therapy group(0% vs 33.3%,P<0.05).②The mortality of the trauma intensive therapy group was significant lower than the truama conventional therapy group(6.7% vs 46.7%,P<0.05).③The mortality of the scald intensive therapy group and the trauma intensive therapy group,the scald conventional therapy group and the trauma conventional therapy group had no significant difference(P<0.05).Conclusions Compared with the conventional therapy,insulin intensive therapy can significant decrease the expression of NF-κB in the livers and the levels of TNF-a in the serum through matained blood glucose at 3.9-5.6mmol/L. It can stop the excessively inflammatory response,and exert protection to the body.Insulin intensive therapy can significantly increase the chance of survival,reduce the mortality.
Keywords/Search Tags:Diabetic rats, Insulin intensive therapy, Trauma, Scald, Nuclear factor-κB, Tumor necrosis factor-α
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