自发性高血压大鼠脑出血急性期中枢和外周肾上腺素能受体表达与血压调控的相关性研究

目的 观察自发性高血压大鼠(spontaneously hypertensive rat,SHR)脑出血后血压变化以及中枢(脑组织)-肾上腺素能受体(adrenergic receptor,AR)和外周(肾组织)α1A-AR的表达,探讨高血压脑出血急性期α1A-AR和α2A-AR与血压调控的相关性.方法 30只6月龄雄性SHR,随机分为假手术组和脑出血1 d、3 d、7 d和14 d组,每组6只.尾袖法测定血压;尾壳核注入Ⅳ型胶原酶建立脑出血模型;逆转录聚合酶链反应和免疫组织化学染色法检测α2A-AR和α2A-AR mRNA和蛋白表达.结果 脑出血后1 d时血压为(195.4 ±8.39)mm Hg,显著高于出血前的(177.8±8.69)mm Hg(P=0.00)和假手术组的(184.1±3.76)mm Hg(P=0.002),3 d时为(185.3±9.22)mm Hg,较1 d时下降,7 d和14d时分别为(177.7±5.62)mm Hg和(176.67±6.06)mm Hg,基本恢复至出血前水平.肾组织α2A-AR mRNA和蛋白在脑出血后1 d时分别为(0.91±0.013)和(0.944±0.142)%,高于假手术组的(0.89±0.018)和(0.779±0.103)%,3 d时达高峰,为(0.93±0.015)(P=0.008)和(1.526 ±0.296)%(P=0.010);(3)脑出血3 d时脑组织俚α2A-AR mRNA和蛋白为(0.93±0.020)和(2.64±0.293)%,显著高于假手术组的(0.86 ±0.019)(P=0.001)和(1.070±0.155)%(P=0.020)以及脑出血1 d时的(0.87±0.029)(P=0.000)和(1.629±0.488)%(P=0.023).脑出血1 d组～7 d组血压变化与脑组织α2A-AR mRNA吸光度的相关系数r=-0.509(P=0.031),与脑组织α2A-AR蛋白表达容积分数的相关系数r=-0.473(P=0.047).结论 急性脑出血的血压调控可能与脑组织α2A-AR和肾组织α2A-AR表达上调有一定的相关性.

Correlation of expressions of center and peripheral adrenoceptors with blood pressure regulation after acute intracerebral hemorrhage in spontaneously hypertensive rats

Objective To observe the changes of the blood pressure after intracerebral hemorrhage (ICH) in spontaneously hypertensive rats (SHRs) as well as the expressions of α2A-adrenergic receptor (AR) in center (brain tissue) and peripheral (renal tissue) α1A-AR and to investigate the correlation between α1A-AR/α2A-AR and blood pressure regulation in acute hypertensive ICH. Methads A total of 30 six-month-old male SHRs were randomly divided into a sham-operation group and ICH (day 1,3, 7 and 14) groups (n =6 in each group). Blood pressure was measured by the tail-cuff method. Collagenase Ⅳ was injected into caudate-puta-men nucleus to induce a model of ICH. The expressions of α1A-AR and α2A-AR were detected by using immunohistochemistry and reverse-transcription polymerase chain reaction. Results One day after ICH, the blood pressure was 195.4 ± 8.39 mm Hg, and it was significantly higher than 177.8 ± 8.69 mm Hg (P = 0. 000) before ICH and 184. 1 ± 3.76 mm Hg in the sham-operation group (P=0. 002). At day 3 it was 185.3 ±9.22 mm Hg, and it was lower than that at day 1. It was 177.7 ±5.62 mm Hg and 176.7 ±6. 06 mm Hg at day7 and 14 respectively, which almost returned to the normal level before ICH. The α1A-AR mRNA and protein in renal tissue at day 1 after ICH were 0. 91 ±0. 013 and 0. 944 ±0. 142%, respectively, They were higher than 0. 89 ±0. 018 and0. 779 ±0. 103% in the sham-operation group, and they reached the peak (0. 93 ±0.015, P =0.008; 1.526 ± 0.296%, P =0.010) at day 3. The α2A-AR mRNA and protein in brain tissue were 0. 93 ±0. 020 and 2.64 ±0. 293% at day 3 after ICH, and they were significantly higher than 0. 86 ±0. 019 (P =0. 001) and 1. 070 ±0. 155% (P = 0. 020), and0.87 ±0. 029 (P =0. 000) at day 1 after ICH and 1. 629 ±0. 488% (P =0. 023) in the sham-operation group. The changes of blood pressure in the ICH day 1 to day 7 grottos in SHRs and correlation coefficient of α2A-AR mRNA absorbance in brain tissue r was - 0. 509 (P = 0.031), and the correlation coefficient of α2A-AR protein-expression volume fraction in brain tissue r was - 0. 473 (P = 0. 047). Conelusions Regulation of blood pressure during acute ICH may have certain correlation with the up-expressions of α2A-AR in brain tissue and α1A-AR in renal tissue.