Bhardwaj Pooja, Khanna Deepa, Balakumar Pitchai
Cardiovascular Pharmacology Division, Department of Pharmacology, Institute of Pharmacy, Rajendra Institute of Technology and Sciences (RITS), Sirsa, 125 055, Haryana, India.
Cardiovasc Toxicol. 2014 Mar;14(1):41-51. doi: 10.1007/s12012-013-9226-y.
Diabetes mellitus is associated with an induction of vascular endothelial dysfunction (VED), an initial event that could lead to the pathogenesis of atherosclerosis and hypertension. Previous studies showed that catechin, a key component of green tea, possesses vascular beneficial effects. We investigated the effect of catechin hydrate in diabetes mellitus-induced experimental vascular endothelial abnormalities (VEA). Streptozotocin (50 mg/kg, i.p., once) administration to rats produced diabetes mellitus, which subsequently induced VEA in 8 weeks by markedly attenuating acetylcholine-induced endothelium-dependent relaxation in the isolated aortic ring preparation, decreasing aortic and serum nitrite/nitrate concentrations and impairing aortic endothelial integrity. These abnormalities in diabetic rats were accompanied with elevated aortic superoxide anion generation and serum lipid peroxidation in addition to hyperglycemia. Catechin hydrate treatment (50 mg/kg/day p.o., 3 weeks) markedly prevented diabetes mellitus-induced VEA and vascular oxidative stress. Intriguingly, in vitro incubation of L-NAME (100 μM), an inhibitor of nitric oxide synthase, or Wortmannin (100 nM), a selective inhibitor of phosphatidylinositol 3-kinase (PI3K), markedly prevented catechin hydrate-induced improvement in acetylcholine-provoked endothelium-dependent relaxation in the diabetic rat aorta. Moreover, catechin hydrate treatment considerably reduced the elevated level of serum glucose in diabetic rats. In conclusion, catechin hydrate treatment prevents diabetes mellitus-induced VED through the activation of endothelial PI3K signal and subsequent activation of eNOS and generation of nitric oxide. In addition, reduction in high glucose, vascular oxidative stress, and lipid peroxidation might additionally contribute to catechin hydrate-associated prevention of diabetic VEA.
糖尿病与血管内皮功能障碍（VED）的诱导有关，这是一个可能导致动脉粥样硬化和高血压发病机制的初始事件。先前的研究表明，儿茶素作为绿茶的关键成分，具有血管有益作用。我们研究了水合儿茶素对糖尿病诱导的实验性血管内皮异常（VEA）的影响。给大鼠腹腔注射链脲佐菌素（50mg/kg，一次）诱导糖尿病，随后在8周内通过显著减弱离体主动脉环标本中乙酰胆碱诱导的内皮依赖性舒张、降低主动脉和血清亚硝酸盐/硝酸盐浓度以及损害主动脉内皮完整性来诱导VEA。除高血糖外，糖尿病大鼠的这些异常还伴有主动脉超氧阴离子生成增加和血清脂质过氧化。水合儿茶素治疗（50mg/kg/天，口服，3周）显著预防了糖尿病诱导的VEA和血管氧化应激。有趣的是，一氧化氮合酶抑制剂L-NAME（100μM）或磷脂酰肌醇3激酶（PI3K）的选择性抑制剂渥曼青霉素（100nM）的体外孵育显著预防了水合儿茶素诱导的糖尿病大鼠主动脉中乙酰胆碱引起的内皮依赖性舒张的改善。此外，水合儿茶素治疗显著降低了糖尿病大鼠升高的血糖水平。总之，水合儿茶素治疗通过激活内皮PI3K信号以及随后激活eNOS和生成一氧化氮来预防糖尿病诱导的VED。此外，高血糖、血管氧化应激和脂质过氧化的降低可能额外有助于水合儿茶素相关的糖尿病VEA预防。
