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Fibronectin Expression In The Obesity, Type 2 Diabetes Kidney

Posted on:2009-01-18Degree:MasterType:Thesis
Country:ChinaCandidate:R WuFull Text:PDF
GTID:2144360242480226Subject:Clinical Medicine
Abstract/Summary:PDF Full Text Request
Obesity was epidemic in the world now. The World Health Orga- nization considers it is one of the 10 risk factors that induce the burden of disease. With the clinical research data, a number of medical workers have recognized that obesity is a high risk factor of clinical which lead to coronary heart disease,hypertension,hyperlipidemia and sleep apnea syndrome, and other common diseases of old people. Obesity as a risk factor of kidney damage receives increasing attention, the relationship between obesity and Type 2 diabetes mellitus become the study focus of the medical workers now.1 ObjectiveTo investigate the expression of fibronectin(FN ) in obesity and Type 2 diabetes mellitus kidney,and investigate the expression of FN which angiotensinⅡrecepetor blocker(ARB)telmisartan influences.2 MethodsPart I Animal groups, administration, specimen collection(1) 24-week-old male obese Zucker rats and 12-week-old obese db/db rats were used in this study, with lean Zucker rats and lean db/m rats as controls respectively. Immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) methods were used to detect FN mRNA and protein. (2) 40 male Wistar rats, one week after the adaptabilitily feeding, 30 rats selected randomly to be given high-fat diet; another 10 of the normal rats (Here it was marked as group C) continued to be given normal diet. A month later, the high-fat diet rats became obese;Body weight was significantly higher than the normal. 10 rats selected randomly from the 30 obese rats as the obese(Here it was marked as OB) group. The other 20 rats were injected STZ of 30 mg / kg by intraperitoneal, OB and C had the same volume of intraperitoneal injection of sodium citrate - ning meng acid buffer. 48 hours after the injection of STZ , measured the random blood glucose.The rats that the blood glucose higher than 300.6mg/dl were the successful models. These diabetic rats were divided into 2 groups : type 2 diabetes(Here it was marked as ODM),medication group (Here it was marked as ODT).The rats of ODT group were given telmisartan of 4 mg/ Kg/d dissolved in distilled water on agavage. We tested the urine albumin quantitative in 24-hour before they were sacrificed. After sacrificed,we took out the kidney and observed the pathological changes. Immunohistochemistry and RT-PCR methods were used to detect FN mRNA and protein.PartⅡStatistical analysisData was presented as Mean±SD, statistical analysis was performed using LSD-t test, P<0.05 or P<0.01 was considered significantly.3 Results(1)Compared to the lean controls, obese db/db rats showed significant increased body weight and serum glucose level(p<0.01).Similarly,compared to the lean controls, obese Zucker rats showed significant increased body weight(p<0.01), but not serum glucose level. Pathological data showed glomeruli size in obese Zucker rat and db/db mouse is lager than their matched controls.Furthermore, the expression of FN protein also increased in obese Zucker rat and db/db rat glomeurli than their matched controls. RT-PCR indicated the expression of FN mRNA is increased in both obese Zucker rat and db/db rat cortical tissue than their matched controls(p<0.01).(2)Compared to C, ODM and ODT rats showed significant increased serum glucose level and body weight were increased significantly(p<0.01). Compared to C, ODM rats showed significant increased kidney weight level(p<0.01). Compared to ODM , ODT rats showed significant decreased kidney weight level(p<0.01). Compared to C, OB rats showed a increasing trend of 24-hour urinary albumin,but not statistically significant (P> 0.05). Compared to C, ODM rats showed significant increased 24-hour urinary albumin level(p<0.01). Compared to ODM,ODT rats showed significant decreased 24-hour urinary albumin level(p<0.01). Pathological data showed the increased size of glomcruli and the light hyperplasia of glomerular mesangial matrix in OB .It also showed the increased size of glomcruli and the severe hyperplasia of glomerular mesangial matrix in ODM . The above-mentioned change in ODT was lighter than which was in ODM . The expression of FN protein increased in rat glomeurli of OB,ODM,ODT than which was in C.The expression of FN protein decreased in rat glomeurli of OB,ODT than which was in ODM .RT-PCR indicated the expression of FN mRNA was increased in cortical tissue of the OB,ODM,ODT than which was in C (p<0.01),and the expression of FN mRNA was decreased in cortical tissue of ODT than which was in ODM(p<0.01).4.Conclusions:(1) Obesity alone can lead to renal fibrosis.(2) Obesity can lead to insulin resistance and it is the risk factor of type 2 diabetes mellitus.(3) The kidney injury of type 2 diabetes mellitus is also renal fibrosis, it is severer than the simple obesity.(4) By rivalring RAS system, ARB reduce the degree of renal fibrosis of type 2 diabetes mellitus.
Keywords/Search Tags:Obesity, Type 2 diabetes mellitus, Fibronectin
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