性别对肾血管性高血压大鼠血压及靶器官损伤的影响

Gender specific effect in development of renovascular hypertension

目的探讨性别对肾血管性高血压大鼠血压及靶器官损伤的影响。方法将160只10周龄健康无特定病原级(SPF)雌雄各半Sprague-Dawley(SD)大鼠随机分为4组,分别为雄性假手术(2K1C-male-sham)组、雄性手术(2K1C-male)组、雌性手术(2K1C-female)组和雌性去势手术(2K1C-OVX)组,每组40只。狭窄一侧肾动脉制备肾血管性高血压模型(2K1C),40只雌性大鼠完成2K1C手术后,摘除双侧卵巢建立雌激素低下模型(OVX)。常规喂养32 w,麻醉状态下颈动脉插管测定血压,取血制备血浆和血清,采用酶联免疫吸附试验(ELISA)测定血液中内皮素(ET-1)、血管紧张素Ⅱ(AngⅡ)、白介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)的含量;测定主要靶器官指数评价靶器官的损伤程度。结果 2K1C组收缩压(SBP)与舒张压(DBP)明显高于2K1C-male-sham组(P<0.05),2K1C-female组的SBP与DBP明显高于2K1C-male组和2K1C-OVX组(P<0.05)。2K1C组的心室指数(VW/BW)、左心室指数(LVW/BW)和肾脏指数(RKW/BW)高于2K1C-male-sham组(P<0.05),2K1C-female组的VW/BW、LVW/BW和RKW/BW高于2K1C-male组和2K1C-OVX组(P<0.05);2K1C-male组的血管指数(AW/L)高于2K1C-male-sham组(P<0.05)。2K1C-male组血浆Ang II高于2K1C-male-sham组(P<0.05);2K1C组血浆ET-1高于2K1C-male-sham组(P<0.05),与2K1C-female组比较,2K1C-male组和2K1C-OVX组的血浆ET-1降低(P<0.05)。2K1C-OVX组血清IL-6的浓度也低于2K1C-female组和2K1C-male组(P<0.05);与2K1C-male-sham组比较,2K1C组血清TNF-α升高(P<0.05)。结论雌性肾血管性高血压大鼠的血压水平及靶器官损伤比雄性大鼠严重。

Objective To evaluate sex specific effect on the development of renovascular hypertension.Methods 160 10-week-age SPF level SD rats were divided into four groups:two kidney one clip(2K1C)sham(2K1C-male-sham)group,2K1C-male group,2K1C-female group and 2K1C-OVX(ovariectomized)group for 40 rats in each group.The rats underwent clipping of the right renal artery or sham operation to develop two-kidney one-clip(2K1C)model of renovascular hypertension.Experiments were carried out for 32 weeks after clipping.Arterial catheterization were used for blood pressure measurement in anesthesia state.The blood was collecting for determination of plasma AngiotensinⅡ(AngⅡ)and endothelin-1(ET-1),serum inflammatory factors by ELISA kits and target organ damage was observed.Results Compared with the 2K1C-male-sham group,SBP and DBP significantly increased in all 2K1C rats(P<0.05).SBP and DBP in the 2K1C-female group were significantly higher than that in the 2K1C-male group and 2K1C-OVX group(P<0.05).Ventricle weight/body weight(VW/BW),left ventricle weight/body weight(LVW/BW)and right kidney weight/body weight(RKW/BW)significantly increased in all 2K1C groups(P<0.05).VW/BW,LVW/BW and RKW/BW in the 2K1C-female group were significantly higher than that in the 2K1C-male group and 2K1C-OVX group(P<0.05).Compared with the 2K1C-male-sham group,aortic weigh/lengtht(AW/L)significantly increased in the 2K1C-male group(P<0.05).Plasma AngⅡwas higher in the 2K1C-male group(P<0.05),and ET-1 was higher in the 2K1C-female group(P<0.05),serum Interleukin-6(IL-6)significantly decreased in the 2K1C-OVX group(P<0.05)and had no change in other groups.And serum tumor necrosis factor-α(TNF-α)significantly increased in all 2K1C groups(P<0.05).Conclusion Female renovascular hypertensive rats have higher blood pressure and more serious target organ damage than those in male rats.