抑郁对自发性高血压大鼠水通道蛋白-2的影响

目的探讨抑郁对自发性高血压大鼠水通道蛋白2（aquaporin2,AQP2）的影响,并探讨AQP2在高血压中的病理生理作用。方法60只SHR大鼠分为对照组（n=30）和抑郁组（n=30）,两组又各分为两个亚组：对照组非药物治疗亚组（n=15）、对照组贝那普利治疗亚组（n=15）;抑郁组非药物治疗亚组（n=15）、抑郁组贝那普利治疗亚组（n=15）。另外,选取Wistar Kyoto（WKY）大鼠20只作为正常组大鼠。药物治疗亚组大鼠予贝那普利10 mg.d-1.kg-1灌胃。抑郁组大鼠采用慢性不可预计温和应激（CUMS）结合行为学指标建立自发性高血压大鼠并抑郁动物模型。对照组、正常组大鼠动物正常饲养。检测并比较各组大鼠间血压的变化及血管加压素和肾脏AQP2表达的差异。结果 （1）抑郁组非药物治疗亚组血压（175±14）mm Hg高于对照组非药物治疗亚组（160±11）mm Hg及正常组（112±9）mm Hg,差异有统计学意义（P〈0.05）;贝那普利治疗后,抑郁组治疗亚组血压（136±15）mm Hg、对照组治疗亚组（113±12）mm Hg均低于各自非药物治疗组（P〈0.05）。（2）抑郁组非药物治疗亚组与正常组、对照组非药物治疗亚组及对照组贝那普利治疗亚组比较,糖水偏爱性均减低（P〈0.05）,体质量和旷场实验评分均明显下降（P〈0.05）,血浆血管加压素浓度升高[（9.31±0.42）pg/mL vs.（1.6±0.67）pg/mL、（3.04±0.97）pg/mL、（2.34±0.91）pg/mL,P〈0.05],AQP2蛋白表达增加（0.95±0.12 vs.0.12±0.07、0.44±0.06、0.24±0.06,P〈0.05）。（3）抑郁组贝那普利治疗亚组与对照组非药物治疗亚组、对照组贝那普利治疗亚组比较,糖水偏爱性均减低（P〈0.05）,体质量和旷场实验评分均明显下降（P〈0.05）,血浆血管加压素浓度升高[（4.55±0.69）pg/mL vs.（3.04±0.97）pg/mL、（2.34±0.91）pg/mL,P〈0.05],AQP2蛋白表达增加（0.62±0.17 vs.0.12±0.07、0.44±0.06,P〈0.05）。（4）对照组贝那普利治疗亚组与抑郁组非药物治疗亚组比较,糖水偏爱性亦增加（P〈0.05）,体质量和旷场实验评分升高（P〈0.05）,血浆AVP浓度下降[（4.55±0.69）pg/mL vs.（9.31±0.42）pg/mL,P〈0.05],AQP2蛋白表达减少（0.62±0.17 vs.0.95±0.12,P〈0.05）。结论抑郁可以促进自发性高血压大鼠血管加压素的分泌及肾脏AQP2的表达。抑郁可能通过促进血管加压素的分泌及肾脏AQP2的表达影响高血压的发展。

Effect of depression on aquaporin-2 in spontaneously hypertensive rats

Objectives To study the effect of depression on aquaporin-2(AQP2) in spontaneously hypertensive rats and the physiological and pathological role of AQP2 in hypertension.Methods Sixty spontaneously hypertensive rats(SHRs) were divided into two groups: depression group(n=30) and control group(n=30).The 2 groups were further divided into two subgroups respectively: benazepril control subgroup(n=15) and no-treatment control subgroup(n=15);benazepril depression subgroup(n=15) and no-treatment depression subgroup(n=15).Meanwhile,20 Wistar-Kyoto(WKY) rats were selected as normal control group.SHRs in benazepril subgroups were taken benazepril 10 mg·d-1·kg-1 by intragastric administration.Models of SHRs in depression group were established by chronic unpredictable mild stress(CUMS) with combination of behavioral indexes.Rats in control group and normal control group were raised normally.Changes of blood pressure,expressions of renal AQP2 and plasma arginine vasopressin(pAVP) of rats in each group were measured and compared.Results(1) Blood pressure in no-treatment depression subgroup(175±14)mm Hg was significantly higher than those in normal control group(112±9)mm Hg and no-treatment control subgroup(160±11)mm Hg(P<0.05).After benazepril treatment,blood pressure in the 2 benazepril subgroups [(136±15)mm Hg in benazepril depression subgroup and(113±12)mm Hg in benazepril control subgroup] were significantly lower than those in no-treatment subgroups(P<0.05).(2) Rats in no-treatment depression subgroup showed a decreased preference for sucrose solutions(P<0.05),a significant reduction in body weight and scores from the open-field test(P<0.05),an increased pAVP concentration [(9.31±0.42)pg/mL vs.(1.6±0.67)pg/mL,(3.04±0.97)pg/mL,(2.34±0.91)pg/mL;P<0.05] and an increased expression of renal AQP2(0.95±0.12 vs.0.12±0.07,0.44±0.06,0.24±0.06;P<0.05) when compared with those in normal control group,no-treatment control subgroup and benazepril control subgroup.(3)Rats in benazepril depression subgroup showed a decreased preference for sucrose solutions(P<0.05),a significant reduction in body weight and scores from the open-field test(P<0.05),an increased pAVP concentration [(4.55±0.69)pg/mL vs.(3.04±0.97)pg/mL,(2.34±0.91)pg/mL;P<0.05] and an increased expression of renal AQP2(0.62±0.17 vs.0.12±0.07,0.44±0.06;P<0.05) when compared with those in no-treatment control subgroup and benazepril control subgroup.(4)Rats in benazepril control subgroup showed an increased preference for sucrose solutions(P<0.05),an increase in body weight and scores from the open-field test(P<0.05),a decreased pAVP concentration [(4.55±0.69)pg/mL vs.(9.31±0.42)pg/mL,P<0.05] and a decreased expression of renal AQP2(0.62±0.17 vs.0.95±0.12,P<0.05) when compared with those in no-treatment depression subgroup.Conclusions Depression can impact the pathogenesis of hypertension by increasing secretion of pAVP and expression of renal AQP2.