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作 者:田登科[1] 陈刚领[1] 李亚娟[1] 胡送友[1] 刘俊[1] 卞卡[1,2]
机构地区:[1]上海中医药大学穆拉德中药现代化研究中心,上海201203 [2]美国德克萨斯大学休斯顿医学院综合生物及药理学系,德克萨斯大学分子医学研究所
出 处:《辽宁中医药大学学报》2009年第6期5-8,共4页Journal of Liaoning University of Traditional Chinese Medicine
基 金:国家科技部十一五支撑计划(2006BAI11B08-03);上海市科委基础研究重点项目(05JC14056)
摘 要:目的:观察麝香保心丸(HMP)对自发性高血压大鼠(SHR)肾脏炎症状态的影响,探讨其对高血压肾脏疾病的防治作用及机制。方法:将6周龄SHR分为HMP治疗组和高血压模型对照组,以同周龄的Wistar-Kyoto(WKY)大鼠为正常对照,在3个时间点(给药6周,给药14周,停药9周)研究HMP对SHR血压值、肾脏炎性因子表达和氧化应激水平的影响。结果:在整个实验过程中HMP对SHR无明显降压作用(P>0.05)。HMP在mRNA和蛋白水平抑制了细胞间粘附分子-1(ICAM-1)和诱导型一氧化氮合酶(iNOS)在SHR肾脏的高表达(P<0.05),在mRNA水平抑制了肿瘤坏死因子-α(TNF-α)的高表达(P<0.05)。HMP在给药14周和停药9周时降低了过氧化物酶体增殖物活化受体γ(PPARγ)的mRNA表达(P<0.05),而在给药6周和给药14周时明显降低了PPARγ的蛋白表达(P<0.05)。HMP给药14周及停药9周后均可显著提高SHR肾脏组织总抗氧化能力(P<0.05),给药14周时能显著降低SHR肾脏组织蛋白羰基化水平(P<0.05)。结论:HMP给药后能够显著减轻SHR肾脏炎症反应,并且伴随着肾脏氧化应激水平的降低,这可能是HMP在防治高血压肾病方面具有应用潜能的作用机理。Objective: To investigate the effect of Heart-protecting Musk Pill ( HMP )on inflammatory status of the kidney from spontaneously hypertensive rat (SHR), and to explore preventive and therapeutic usage of HMP on hypertensive nephropathy. Methods: SHR of 6 weeks old were divided into HMP group,high blood pressure model group, and-age-matched Wistar-Kyoto rats were used as normal control. The effects of HMP on systolic blood pressure, expression of inflammation-related factors and level of oxidative stress were determined at 3 time points: 6 weeks of treatment; 14 weeks of treatment; and 9 weeks post-treatment. Results: HMP did not inference the elevation of blood pressure of SHR through period of treatment(P〉0.05).However, the TCM compound inhibited the expression of intercellular adhesion molecule-1 (ICAM-1) and inducible nitric oxide synthase (iNOS) at both mRNA and protein levels (P〈0.05). HMP also inhibited the mRNA expression of turner nerosis factor-α (TNF-α) in SHR kidney (P〈0.05). At the time points of 14 weeks of treatment and 9 weeks post-treatment, HMP significantly attenuated peroxisome proliferatoractivated receptor γ/(PPAR γ ) mRNA expression(P〈0;05). The protein level of PPAR γ was also inhibited by HMP markedly after 6 and 14 weeks of treatment(P〈0.05). After 14 weeks of treatment, HMP increased total anti-oxidant capacity of renal tissue from SHR (P〈0.05) and this elevated anti-oxidant capacity was even maintained for 9 weeks post-treatment (P〈0.05). In addition, HMP 14 week of treatment significantly reduced protein carbonyl contents of SHR kidney (P〈0.05). Conclusion: HMP can improve the inflammatory status of SHR kidney independent of interfering with blood pressure. The anti-inflammatory effect of HMP was also acccmpanied by the decreasing level of oxidative stress, which may serve base for the advanced therapeutic utility of HMP in hypertensive renal disease.
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