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目的探讨水通道蛋白4(AQP4)在1,2-二氯乙烷(1,2-DCE)亚急性吸入所致中毒性脑水肿发生中的作用。方法无特定病原体级健康成年雌性SD大鼠,随机分为对照组(8只)、低剂量组(12只)和高剂量组(12只)。采用口鼻式动式吸入法染毒,3组大鼠1,2-DCE染毒剂量分别为0、600和1 800 mg/m3,连续7 d,8.0 h/d。染毒结束后,取大脑皮质行病理组织学检查,采用实时荧光定量聚合酶链反应法检测大脑皮质组织中基质金属蛋白酶2(MMP2)、钠-钾-氯共转运体1(NKCC1)、AQP4的mRNA相对表达水平,采用免疫印迹法检测大脑皮质组织中AQP4蛋白相对表达水平。结果病理组织学检查结果显示,低剂量组大鼠可见大脑皮质血管周围组织疏松,血管组织间隙扩大;高剂量组大鼠可见较明显的大脑皮质或血管周围组织疏松和空泡,程度较低剂量组严重。分别与对照组及低剂量组比较,高剂量组大鼠大脑皮质MMP2 mRNA相对表达水平均升高[(1.07±0.41)vs(1.56±0.55),(1.21±0.59)vs(1.56±0.55),P<0.05],AQP4 mRNA相对表达水平均下降[(1.03±0.25)vs(0.81±0.12),(1.00±0.20)vs(0.81±0.12),P<0.05];3组大鼠大脑皮质NKCC1 mRNA相对表达水平比较,差异无统计学意义[(1.03±0.31)vs(1.14±0.43)vs(1.36±0.50),P>0.05]。高剂量组大鼠大脑皮质AQP4蛋白相对表达水平低于对照组[(0.80±0.25)vs(1.19±0.42),P<0.05]。结论 1,2-DCE亚急性吸入所致大鼠脑水肿是以血管源性为主的混合型脑水肿,其发病机制与AQP4的表达量改变有关。
Objective To investigate the role of aquaporin 4 (AQP4) in the pathogenesis of toxic brain edema induced by subacute inhalation of 1,2-dichloroethane (1,2-DCE). Methods Healthy adult female SD rats without specific pathogen were randomly divided into control group (n = 8), low dose group (n = 12) and high dose group (n = 12). The rats were anesthetized by buccal and inhalation inhalation. The doses of 1,2-DCE in the three groups were 0,600 and 1 800 mg / m3 for 7 days and 8.0 hours respectively. After the exposure, the cerebral cortex was taken for histopathological examination. The expression of matrix metalloproteinase 2 (MMP2), sodium-potassium-chloride co-transporter 1 (NKCC1) and AQP4 in the cerebral cortex were detected by real-time fluorescence quantitative polymerase chain reaction MRNA relative expression levels of the AQP4 protein in cerebral cortex were detected by Western blotting. Results The histopathological examination showed that the peri-vascular tissue around the cerebral cortex was loosened and the gap of vascular tissue was enlarged in the low-dose group. In the high-dose group, obvious cerebral cortex or perivascular tissue was found to be loose and vacuolated, and the lower dose Serious group. Compared with the control group and the low-dose group, the relative expression level of MMP2 mRNA in the cerebral cortex of high-dose group was significantly higher than that of the control group and the low-dose group (1.07 ± 0.41 vs 1.56 ± 0.55, 1.21 ± 0.59 vs 1.56 ± 0.55, (P0.01 ± 0.12), (1.00 ± 0.20) vs (0.81 ± 0.12), P <0.05]. The expressions of NKCC1 mRNA in the cerebral cortex (1.03 ± 0.31) vs (1.14 ± 0.43) vs (1.36 ± 0.50), P> 0.05, respectively. The relative expression of AQP4 protein in cerebral cortex of high dose group was lower than that of control group [(0.80 ± 0.25) vs (1.19 ± 0.42), P <0.05]. Conclusions The cerebral edema induced by 1,2-DCE induced by subacute inhalation in rats is a mixed-type brain edema predominantly of vasculogenic origin. The pathogenesis is related to the change of the expression of AQP4.