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Acid-flux Adjustment Method Study On Mechanisms Of Prevention And Treatment Of Insulin Resistance In OLETF Rats

Posted on:2012-04-05Degree:DoctorType:Dissertation
Country:ChinaCandidate:M YuFull Text:PDF
GTID:1114330338962278Subject:Chinese medical science
Abstract/Summary:PDF Full Text Request
Objective: This subject is discussed from the adipose tissue inflammation and lipid metabolism disorders in type 2 diabetes mellitus (T2DM), insulin resistance (IR), adopted acid-flux adjustment method to intervene adipose tissue inflammation pathways and lipid metabolism of spontaneity of type 2 diabetic rats (OLETF rat).From the molecular level,it demonstrated acid-flux adjustment method regulate lipid metabolism pathway AMPK activity, cut steroids to regulating elements combined with protein (SREBPs) expression, improve the body inflammation, fat metabolism disorders, so as to intervene T2DM and IR. To explain the Traditional Chinese medicine connotation of " acid-flux adjustment method ", and reveal the acting targets of " acid-flux adjustment method ",so as to providing new ideas and methods to prevention and cure insulin resistance(IR) in obese patients with T2DM.Methods: A control study was carried out between the spontaneous Type 2 Diabetes Mellitus rat(sOLETF rats)and LETO rats,and all OLETF rats were divided into three groups randomly:Model group,Metformin group and KuSuanTongTiao Prescription group.Studies were as follows:1,Blood glucose,lipid and insulin resistance related indexes were determined.2,detecting the levels of serum TNF-α,IL-6,CRP of OLETF rats By the method of ELISA.3,Immunohistochemical method and real-time flourescent quantitative polymerase chain reaction(PCR)technology were used to detect the expression of Mcp-1,PAI-1 in adipose tissue from the protein and gene levels in each group.4,Using HE staining method to observe the ectopic accumulation of lipid, Using GENMED to observe AMPK activity, and immunohistochemical method and real-time flourescent quantitative polymerase chain reaction(PCR)technology were used to detect the expression of SREBPs in OLETF rat's liver.Results: 1,The influence about KuSuanTongTiao Prescription in the OLETF rats. The results showed (1)The KuSuanTongTiao Prescription could significantly reduce the body weight of OLETF rats,reduce intra-abdominal fat content, and owned better therapeutic effect of weight reduction. (2)The KuSuanTongTiao Prescription could significantly reduce blood glucose,TG,TC and FFA levels of OLETF rats,increase steady-state GIR. It had better role of decreasing blood glucose,regulating lipid and improving the IR. 2,The influence about KSTT Prescription on the levels of serum inflammatory factors (TNF-α,IL-6,CRP )of OLETF rats.The results showed the levels of serum TNF-α,IL-6,CRP in Model group significantly increased, KSTT Prescription could significantly reduce the levels of inflammatory factors. 3,The study about effect of KuSuanTongTiao Prescription on Mcp-1,PAI-1 protein and mRNA of OLETF rats.The results showed the expression of Mcp-1,PAI-1 in Model group increased,which in KuSuanTongTiao's Prescription group decreased. 4,The influence about effect of KSTT Prescription on the AMPK activity and SREBPs expression in OLETF rat's liver. The results showed that KSTT Prescription can regulate the lipid metabolism level of OLETF and reduce the ectopic accumulation of lipid may by regulating the liver AMPK activity and some important Rate-limited Enthymemes related to lipid metabolism.Conclusions: Now it is widely recognizied that insulin resistance(IR)andβ-cell secretory dysfunction are the two significant links in the T2DM pathogenesis,and IR is considered to be the initiating agent which lead to T2DM,and throughout the whole process of the T2DM occurrence and development. The topic combining ancient and modern literatures of traditional Chinese medicine and tutor's clinical practice, put forward "six yu and collaterals sluggish", "poison damage of fat venation" is the Chinese medicine key pathogenesis for obesity T2DM, IR .,produced a academic viewpoint that disorder of lipid metabolism and inflammation of adipose tissue might be considerable reason for causing IR,thereby leading to T2DM. The experimental study clarifies Mcp-1,PAI-1 inflammatory expression of T2DM rats'adipose tissue,and regulating the lipid metabolism level by regulating the AMPK activity to increase expression of SREBPs protein and mRNA,so as to providing new ideas and methods to prevention and cure insulin resistance(IR) in obese patients with T2DM.
Keywords/Search Tags:Type 2 diabetic mellitus, Insulin resistance, inflammatory pathogenesis, disorder of lipid metabolism, KuSuanTongTiao, Experimental study
PDF Full Text Request
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