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目的探讨水摄入不足时脑梗死大鼠梗死灶周围组织水通道蛋白4(aquaporin-4,AQP4)表达和脑水肿变化及其对脑梗死程度的影响。方法 SD大鼠96只随机分为假手术组、对照组、实验1组和实验2组各24只。假手术组和对照组正常进食、饮水;实验1组禁水1d,实验2组禁水3d,正常进食。实验1组、实验2组和对照组采用线栓法制备脑梗死模型,假手术组不插入线栓。分别于造模成功后6h及1、2、3d测定4组脑含水量;采用ELISA法检测AQP4表达水平;采用TTC染色法计算脑梗死灶体积,Pearson相关分析AQP4表达与脑含水量的相关性。结果造模后6h及1、2、3d,脑组织含水量在对照组[(76.35±0.02)%、(76.78±0.24)%、(81.03±0.08)%、(80.66±0.21)%]、实验1组[(76.59±0.06)%、(77.32±0.17)%、(81.66±0.28)%、(81.04±0.05)%]和实验2组[(76.82±0.21)%、(77.94±0.17)%、(81.97±0.06)%、(81.49±0.18)%]高于假手术组[(76.06±0.09)%、(75.95±0.07)%、(76.04±0.07)%、(76.00±0.12)%],且实验2组高于实验1组和对照组,实验1组高于对照组(P<0.05);造模成功后6h及1、2、3d,AQP4蛋白水平在对照组[(22.43±0.10)、(24.36±0.10)、(24.95±0.17)、(32.25±0.20)μg/L],实验1组[(22.74±0.04)、(24.92±0.13)、(25.26±0.08)、(33.28±0.18)μg/L]和实验2组[(23.10±0.12)、(25.18±0.12)、(25.49±0.06)、(34.00±0.12)μg/L]高于假手术组[(13.65±0.23)、(13.74±0.17)、(13.92±0.12)、(13.97±0.08)μg/L],且实验2组高于实验1组和对照组,实验1组高于对照组(P<0.05);造模后6h及1、2、3d,假手术组无梗死灶,对照组脑梗死灶体积为[(98.15±0.07)、(114.51±0.13)、(131.62±0.26)、(150.18±0.22)mm3],实验1组为[(168.08±0.12)、(181.11±0.12)、(202.12±0.13)、(220.11±0.16)mm3],实验2组为[(192.12±0.21)、(223.12±0.16)、(240.00±0.17)、(263.10±0.14)mm3],实验2组脑梗死体积大于实验1组和对照组,实验1组大于对照组(P<0.05);Pearson相关分析结果显示,假手术组脑组织含水量与AQP4表达水平无线性相关(r=-0.203,P=0.527),对照组、实验1组和实验2组脑组织含水量均与AQP4水平呈线性相关(r=0.667,P=0.018;r=0.625,P=0.030;r=0.623,P=0.031)。结论水摄入不足可促进脑梗死周围组织AQP4蛋白表达,引起脑水肿,导致脑梗死程度进一步加重。
Objective To investigate the changes of aquaporin-4 (AQP4) expression and cerebral edema in infarcted peri-infarct tissues in rats with cerebral infarction and their effect on cerebral infarction. Methods Ninety-six SD rats were randomly divided into sham operation group, control group, experimental group 1 and experimental group 2, 24 rats in each group. Sham-operation group and control group normal eating, drinking water; experimental group 1 water for 1 day, experimental group 2 forbidden water 3d, normal eating. The experimental group 1, the experimental group 2 and the control group were prepared by the method of thread occlusion cerebral infarction model, sham operation group without thread plug. The brain water content of 4 groups was measured at 6h, 1, 2 and 3 days after model making success. The expression of AQP4 was detected by ELISA. The volume of cerebral infarction was calculated by TTC staining. The correlation between AQP4 expression and brain water content was analyzed by Pearson correlation analysis . Results The water content of brain tissue in the control group was (76.35 ± 0.02)%, (76.78 ± 0.24)%, (81.03 ± 0.08)%, (80.66 ± 0.21)% at 6h, (76.82 ± 0.21)%, (77.92 ± 0.17)%, (81.66 ± 0.28)% and (81.04 ± 0.05)% in group 1 and (76.82 ± 0.21)% and (77.94 ± 0.17)% in group 2, (81.9 ± 0.06)% and (81.49 ± 0.18)%, respectively, which were significantly higher than those in the sham-operation group (76.06 ± 0.09%, 75.95 ± 0.07%, 76.04 ± 0.07%, 76.00 ± 0.12% The level of AQP4 protein in control group was significantly higher than that in control group [(22.43 ± 0.10), P <0.05], and the level of AQP4 protein in control group [(22.43 ± 0.10) (24.36 ± 0.10), (24.95 ± 0.17) and (32.25 ± 0.20) μg / L, respectively. The levels of [(22.74 ± 0.04), (24.92 ± 0.13), (25.26 ± 0.08), (33.28 ± 0.18) μg / L] and (23.18 ± 0.12) and (25.18 ± 0.12) and (34.00 ± 0.12) μg / L in the experimental group 2 were significantly higher than those in the sham operation group [(13.65 ± 0.23) and (13.74 ± 0.17), (13.92 ± 0.12) and (13.97 ± 0.08) μg / L, respectively. The experimental group 2 was higher than the experimental group 1 and the control group, and the experimental group 1 was higher than the control group (P <0.05) 1,2,3d, sham-operated group without infarction, cerebral infarction volume in control group [(98.15 ± 0.07), (11 4.51 ± 0.13, 131.62 ± 0.26, and 150.18 ± 0.22 mm3, respectively. The differences between the two groups were statistically significant (P <0.01) In the experimental group 2, the volume of cerebral infarction in experimental group 2 was larger than that in experimental group 1 and the control group, while that in experimental group 1 was larger than that in control group (192.12 ± 0.21), (223.12 ± 0.16), (240.00 ± 0.17) and (263.10 ± 0.14) mm3 (P <0.05). The results of Pearson correlation analysis showed that there was no linear correlation between the water content of brain tissue and the expression of AQP4 in sham-operated group (r = -0.203, P = 0.527) Water content was linearly correlated with AQP4 level (r = 0.667, P = 0.018; r = 0.625, P = 0.030; r = 0.623, P = 0.031). Conclusions Insufficient water intake can promote the expression of AQP4 protein in peripheral tissues around cerebral infarction and cause cerebral edema, which further aggravates the degree of cerebral infarction.