罗格列酮对高血压大鼠的肾保护作用及其与血管紧张素Ⅱ受体表达的关系

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50 µg·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。

Renal protection of rosiglitazone in hypertensive rats and its relationship with the expression of angiotensin Ⅱ receptor

Objective To observe the role of rosiglitazone in unclipped kidneys of two-kidney- one-clip hypertensive rats and examine its relationship to angiotensin Ⅱ receptors. Methods Two-kidney-one-clip hypertensive rats were divided randomly into 4 groups as follows: positive control group (CONT)， traditional antihypertensive drugs group (TAHD， reserpine 50 µg·kg^-1·d^-1， dihydralazine 6.25 mg·kg^-1·d^-1 and hydrochlorothiazide 6.25 mg·kg^-1·d^-1， regular-dose rosiglitazone group (RRGL， rosiglitazone 5 mg·kg^-1·d^-1)， and high-dose rosiglitazone group (HRGL， rosiglitazone 20 mg·kg^-1·d^-1). Sham operation rats were as negative controls. Each group had 8 rats. Animals were monitored and sacrificed at 10th week. Results Blood systolic pressure in TAHD group and HRGL group was significantly lower than that in CONT group [TAHD(137±27 ) mm Hg and HRGL(143±16) mm Hg vs CONT (191±25) mm Hg， P < 0.05]， but no significant difference between the former two groups was found. Nor did the blood systolic pressure between RRGL group [(176±18) mm Hg] and CONT group. At 10th week， rats in SHAM group and treated groups had lower urinary urinary protein excretion rate， glomerular injury score and wall-to-lumen ratio of arteriole than those in CONT group[vs CONT urinary protein excretion rate (44.60±17.40) mg/24 h， P < 0.05； vs CONT glomerular injury score 60.85±33.05， P < 0.05； vs CONT wall-to-lumen ratio of arteriole 2.33±1.01， P < 0.01，except TAHD group]. Though with the similar level of blood pressure， blood glucose and lipid， HRGL， compared with TAHD group showed lower urinary protein excretion rate [HRGL (16.78±3.50) mg/24 h vs TAHD (27.94±12.79) mg/24 h， P < 0.05]， decreased glomerular injury score (HRGL 18.04±7.76 vs TAHD 27.92±6.39， P < 0.05) and wall-to-lumen ratio of arteriole (HRGL 1.75±0.38 vs TAHD 2.16±0.90， P < 0.05) in the cortexes of unclipped right kidneys. The expression of type 1 angiotensin Ⅱ receptor (AT1R) mRNA was no difference in HRGL group and TAHD group， but the expression of type 2 angiotensin Ⅱ receptor (AT2R) mRNA was more intensive in HRGL group. Conclusion Rosiglitazone can protect the kidneys from hypertensive injury， especially in high dose. The beneficial effects seem incompletely dependent on the metabolism modulating and reduction of blood pressure， but in relationship to the upregulation of AT2R mRNA.