氧化应激应激ppt参考课件.ppt

# * One reason is that although antioxidant supplementation can be effective with aproved methodology for oxidative stress, we are still unable to deduce a priori those subjects who will be responders or nonresponders. Another reason for antioxidant ineffectiveness could relate to the optimum dose and type of antioxidants being used; efficacious threshold doses have been suggested at 800 IU/d of RRR-AT and 500 mg/d of AA.127,134 However, a key issue is antioxidant formulation; 5 of 7 antioxidant supplementation trials that reported inefficacy on primary end points used all-racemic-AT (all-rac-AT), but 4 trials described above with successful results used RRR AT. 127 The third reason why antioxidants are not yet successful in CVD prevention could be the complexity of redox reactions in vivo and the potential for a paradoxical increase in oxidant generation by antioxidants themselves. For instance, vitamin C supplementation exerted prooxidant as well as antioxidant effects in healthy volunteers; however, high doses of this antioxidant increased DNA damage.135 It was hypothesized that transition metal ions, released from metalloproteins after initial oxidative stress, act as catalysts in the presence of antioxidants to exacerbate the free radicalinduced damage.13 Oxidative stress and atherosclerosis 氧化应激与 动脉粥样硬化 * # 动脉粥样硬化的血管 * # 动脉粥样硬化临床分期 无症状隐匿期：粥样硬化斑块已形成，但尚无明显狭窄，因此无器官受累临床表现。（脂质条纹多于5~10岁的儿童开始，粥样斑块始见于20岁)。 缺血期：粥样硬化斑块导致血管狭窄、器官缺血，根据累及器官不同临床表现也不同。 坏死期：动脉堵塞或血管腔内血栓形成造成相应器官组织坏死产生的症状。 纤维化期：长期缺血导致相应器官组织纤维化萎缩 * # 动脉粥样硬化脂质氧化理论的提出 脂源性理论无法解释4种现象: LDL-R缺乏的患者(家族性纯合子型高胆固醇血症)或动物模型,由于巨噬细胞表面的LDL-R缺乏,LDL无法通过LDL-R途径被巨噬细胞摄取,但是该类患者或动物模型动脉粥样硬化的发病率几乎是100%。 ? 1 * # 体外试验中,即使将单核-巨噬细胞和平滑肌细胞和浓度非常高的LDL血浆共同培养后,也并不能诱导胆固醇在细胞内的聚积。 ? 2 动脉粥样硬化脂质氧化理论的提出 * # 动脉粥样硬化脂质氧化理论的提出 LDL-R受细胞内胆固醇含量的负反馈调节。LDL和LDL-R结合后,内吞进入巨噬细胞胞浆,与溶酶体结合后,在溶酶体酶的作用下,LDL中的蛋白质降解为氨基酸,而胆固醇酯水解为游离胆固醇和脂肪酸。但是,当细胞内胆固醇的含量饱和时,便会反馈性调节细胞表面的LDL-R的数量减少,功能下调。所以LDL经这一途径代谢只是一个生理过程,并不会引起胆固醇在巨噬细胞内堆积。 ? 3 * # 多个流行病学调查结果显示,动脉粥样硬化与高胆固醇血症之间呈