Nf-¦Êb In The Pathogenesis Of Diabetic Vascular Complications In The Study

PART 1STUDY ON NF- к B ACTIVATION IN THE PATHOGENESIS OF ATHEROSCLEROSIS IN DIABETIC RATSObjective: To explore the role of the activated NF- K B in pathogenesisof the atherosclerosis in diabetic rats and the relation between NF- K Bactivation and the expression of ICAM-1.Methods: Wistar rats were randomly divided into three groups: the control (group C). streptoxotocin-induced diabetic rats (group DM),N-acetylcysteine-treated diabetic rats (group NAQ.After 1,2,3 and 4 months, all rats were killed, respectively,and the following items in the plasma were determined: HbAlC,triglyceride (TG),total cholesterol(TC),high density lipoproteins (HDL).The expression of ICAM-l in aortic endothelium wasmeasured with immunohistochemisty assay.The NF- K B activation wasanalyzed by electrophoretic mobility shift assay(EMSA).Results:1.The levels of blood glucose and HbAlC in group DM and group NAC were significantly elevated as compared with group C.2.The level of blood lipids in group DM and group NAC was notincreased after 1 , 2 months, but was raised after 3 , 4months,respectively ,compared with group C, and not reached the criterion of dyslipidimia.3. NF-к B was significantly activated in diabetic rats after 3, 4months.4. ICAM-1 showed positive expression in aorta of diabetic rats afterraised for 3, 4 months,and the expression of ICAM-1 can be inhibited by NAC.Conclusions: 1. NF-кB is significantly activated in aorta ofdiabetic rats, and induces the expressions of its target genes, such as ICAM-1 and the like,and cause the development of atherosclerosis indiabetic rats .The NF- к B activation may be the key factor leading to the development of atherosclerosis in diabetic rats.2. Antioxidant NAC can inhibit the NF- K B activation and theexpression of its target genes such as adhesion molecules ICAM- 1 Antioxidant may play an important role in preventing the development of atherosclerosis in diabetic rats.3. Hyperglycemia may contribute to the NF- K B activation ,so strictcontrol of hyperglycemia as early as possible may prevent the development of atherosclerosis in diabetic rats.PART 2 STUDY ON NF-кB ACTIVATION IN PBMCsWITH TYPE 2 DIABETIC MACROVASCULAR COMPLICATIONSObjective: We investigate the NF- кB activation in PBMCs in- 9patients with type 2 diabetic macroangiopathy.Methods: We examined 60 patients with type 2 diabetes (30 patients with macroangiopathy ,30 patients without macroangiopathy).40 normalcontrols.The NF- кB DNA binding activity in PBMCs was analyzed by electrophoretic mobility shift assay (EMSA),and the blood glucose, TG, TC, HDL and LDL were determined.Results: In normal controls,the NF- к B activation was notobserved.The NF-к B DNA binding activity in patients with type 2diabetic macroangiopathy was significantly increased compared with that in patients without macroangiopathy.Conclusions: The NF- K B activation is an early responsive index ofdiabetic macroangiopathy, and its activation correlates with hyperglycermia and hyperlipoidemia.Strict control hyperglycermia and hyperlipoidemia is the basement for preventing diabetic complications.PART 3 THE EFFECT OF RECOMBINANT ADENOVIRUS MEDIATEDNF-KB SUPER-REPRESSOR AdlKBaM ON TRANSFECTED HUVECObjective: To explore the effect of recombinant adenovirus. mediated NF-к B super-repressor AdIк B a M on transfected HUVEC.Methods: MTT , 3H-TdR incoporation and FACSC assay methods were used to determine Adi K B a M effect on HUVECs growth . Theeffect of Adi K B a M on the expression and activation of NF- к B of HUVEC was determined by immunohistochemistry and EMSA. The expression of I к B α in AdI к B αa M tansfected HUVEC was assayedby Western Blot method ,and the ICAM-1 and MCP-1 was assayed by RT-PCR and immunohistochemistry methods,respectively.Results: The recombinant adenovirus titers were 2.5 X 109/mI. The quantity of positively transfected HUVEC cells raised with increased MOI. The expression of Iк B α was highe...