本文選題：糖尿病 + 內(nèi)皮��； 參考：《中國藥理學(xué)與毒理學(xué)雜志》2015年04期

【摘要】：目的探討吡咯烷二硫代氨基甲酸鹽(PDTC)對糖尿病大鼠血管內(nèi)皮依賴性舒張功能損害的保護作用及其機制。方法雄性SD大鼠一次性ip給予鏈脲佐菌素60 mg·kg-1制備糖尿病模型,通過飲水中給予PDTC 10 mg·kg-1,連續(xù)治療8周。檢測血糖、血脂和血清內(nèi)源性一氧化氮合酶(NOS)抑制物非對稱性二甲基精氨酸(ADMA)濃度。用含有人二甲基精氨酸二甲胺水解酶2(h DDAH2)基因的重組腺病毒(Ad5CMV-h DDAH2)體外感染糖尿病大鼠血管環(huán),分別檢測感染前后血管環(huán)對乙酰膽堿誘導(dǎo)的最大舒張反應(yīng)(Emax)、半數(shù)有效量(EC50)及血管組織DDAH活性。結(jié)果與正常組比較,糖尿病大鼠血糖明顯升高,血清ADMA濃度從正常組的(1.14±0.26)μmol·L-1升至(2.18±0.52)μmol·L-1(P0.01);血管組織DDAH活性也從正常組的(0.10±0.02)U·g-1蛋白降至(0.05±0.01)U·g-1蛋白(P0.01);血管內(nèi)皮依賴性舒張功能損傷,表現(xiàn)為Emax由正常組的(93.6±4.4)%降至(50.8±4.9)%(P0.01),EC50由正常組的(88±22)nmol·L-1升至(240±45)nmol·L-1(P0.01)。PDTC治療降低血糖和血清ADMA濃度分別至(13.2±3.5)mmol·L-1和(1.40±0.25)μmol·L-1(P0.01),增加血管DDAH活性至(0.08±0.02)U·g-1蛋白(P0.01),改善內(nèi)皮依賴性血管舒張功能,使Emax增至(84.6±4.5)%,EC50降至(134±27)nmol·L-1(P0.01)。糖尿病大鼠血管轉(zhuǎn)染DDAH2基因后,血管DDAH活性及Emax和EC50的變化與PDTC治療組相似。結(jié)論 PDTC對糖尿病大鼠血管內(nèi)皮依賴性舒張功能具有明顯的保護作用,其機制可能與上調(diào)血管DDAH活性,降低內(nèi)源性NOS抑制物ADMA蓄積有關(guān)。
[Abstract]:Objective to investigate the protective effect and mechanism of pyrrolidine dithiocarbamate (PDTC) on vascular endothelium-dependent diastolic dysfunction in diabetic rats. Methods male Sprague-Dawley rats were given streptozotocin 60 mg kg-1 once by IP for 8 weeks. The diabetic model was treated with PDTC 10 mg kg -1 in drinking water for 8 weeks. Blood glucose, blood lipids and serum endogenous nitric oxide synthase (NOS) inhibitor, asymmetric dimethyl arginine (ADMA), were measured. The vascular rings of diabetic rats were infected with recombinant adenovirus Ad5CMV-h DDAH2 containing the human dimethyl arginine dimethylamine hydrolase 2hDDAH2 gene in vitro. The maximal diastolic response to acetylcholine induced by acetylcholine was measured before and after infection, and the activity of DDAH in vascular tissue was measured. Results compared with the normal group, the blood glucose of diabetic rats was significantly increased, the serum ADMA concentration was increased from 1.14 鹵0.26 渭 mol L-1 to 2.18 鹵0.52 渭 mol L-1 P0.01A, the DDAH activity of vascular tissue decreased from 0.10 鹵0.02U g -1 protein to 0.05 鹵0.01U g -1 protein P0.01a, and the vascular endothelium-dependent diastolic function was damaged. 琛ㄧ幇涓篍max鐢辨甯哥粍鐨，

本文編號：1962974