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目的研究罗格列酮对高血压肾损伤的保护作用,及其与肾内血管紧张素Ⅱ(ATⅡ)受体表达的关系。方法两肾一夹高血压大鼠随机分为:(1)高血压未治疗组;(2)普通降压组(利血平50μg·kg~(-1)·d~(-1)+二肼苯达嗪6.25 mg·kg~(-1)·d~(-1)+氢氯噻嗪6.25 mg·kg~(-1)·d~(-1));(3)常规剂量罗格列酮组(罗格列酮5 mg·kg~(-1)·d~(-1));(4)大剂量罗格列酮组(罗格列酮20 mg·kg~(-1)·d~(-1))。假手术大鼠作为对照。结果常规剂量罗格列酮组收缩压为(176±18)mm Hg,与高血压未治疗组(191±25)mm Hg相比,无显著差异。大剂量罗格列酮组收缩压为(143±16)mm Hg,普通降压组收缩压为(137±27)mm Hg,与高血压未治疗组相比,差异有统计学意义(P<0.05)。在血压、血糖、血脂水平相似的情况下,大剂量罗格列酮组尿蛋白排泄率为(16.78±3.50)mg/24 h,较普通降压组(27.94±12.79)mg/24 h显著降低(P<0.05)。未钳夹侧肾脏病理改变轻,大剂量罗格列酮组肾小球损伤指数为18.04±7.76,与普通降压组27.92±6.39相比,差异有统计学意义(P<0.05):大剂量罗格列酮组微动脉壁/腔比为1.75±0.38,与普通降压组2.16±0.90相比,差异有统计学意义(P<0.05):大剂量罗格列酮组2型血管紧张素Ⅱ受体(AT2R)mRNA表达上调。结论罗格列酮对高血压肾损伤具有保护作用,可能与其上调肾内AT2R表达有关。
Objective To study the protective effect of rosiglitazone on hypertensive renal injury and its relationship with the expression of angiotensin Ⅱ receptor (AT Ⅱ) in the kidney. Methods Two kidneys and one clip hypertensive rats were randomly divided into: (1) hypertensive untreated group; (2) general antihypertensive group (reserpine 50μg · kg -1 · d -1 + (6.25 mg · kg -1 · d -1) and hydrochlorothiazide (6.25 mg · kg -1 · d -1) for hydralazine; (3) (5 mg · kg -1 · d -1) of rosiglitazone group; (4) high dose rosiglitazone group (rosiglitazone 20 mg · kg -1 ) · D -1). Sham-operated rats served as controls. Results The systolic blood pressure of rosiglitazone group was (176 ± 18) mm Hg, which was not significantly different from that of hypertensive group (191 ± 25) mm Hg. The systolic blood pressure of the high-dose rosiglitazone group was (143 ± 16) mm Hg, and the systolic blood pressure of the common antihypertensive group was (137 ± 27) mm Hg, which was significantly higher than that of the untreated hypertensive group (P < 0.05). The urinary protein excretion rate of high dose rosiglitazone group was (16.78 ± 3.50) mg / 24 h, which was significantly lower than that of normal blood pressure group (27.94 ± 12. 79) mg / 24 h significantly reduced (P <0.05). The pathological changes of uninjured kidneys were mild, the glomerular damage index of high-dose rosiglitazone group was 18.04 ± 7.76, which was significantly different from that of common antihypertensive group (27.92 ± 6.39) (P <0.05). The mean arterial wall / lumen ratio of high-dose rosiglitazone group was 1.75 ± 0.38, which was significantly different from that of common blood pressure group (2.16 ± 0.90) (P <0.05). The mRNA expression of type 2 angiotensin Ⅱ receptor (AT2R) in high-dose rosiglitazone group was up-regulated. Conclusions Rosiglitazone has a protective effect on hypertensive renal injury, which may be related to its upregulation of renal AT2R expression.