Effect of soy isoflavones on blood-brain barrier permeability and its mechanism in rats with focal cerebral ischemia-reperfusion injury
Liu Fufeng1,2, Du Xiaowei2,3, Zhou Yongzhi2,3, Liu Sinan2,3, Zhu Mengna2,3, Wei Meng2,3, Jiang Weizhen2,3, Miao Ying2,3, Zhuo Ning2,3, Han Rongrong2,3, Cheng Yuanfeng2,3, Zhao Shidi1,2
1Department of Pathophysiology, Bengbu Medical College, Bengbu 233030,China; 2Research Center, Bengbu Medical College, Bengbu 233030, China; 3Department of Clinical Medicine College, Bengbu Medical College, Bengbu 233030 , China
Abstract:Objective To investigate the effect of soy isoflavones (SI) on blood-brain barrier (BBB) permeability in rats with focal cerebral ischemia reperfusion and the related mechanism.Methods A total of 72 healthy adult SD rats were randomly divided into sham operation group (Sham group), ischemia-reperfusion group (I/R group), and SI pretreatment group (SI group), with 24 rats in each group. The SI group was intragastrically administered with SI 120 mg/kg according to body weight once a day for 21 days, and the other two groups were intragastrically administered with an equal volume of normal saline once a day for 21 days. On day 22, the rat model of middle cerebral artery ischemia/reperfusion was established by blocking the blood flow of the right middle cerebral artery with thread embolism in the I/R and SI groups. In the Sham group, no thread embolism was inserted and blood flow was not blocked. The remaining steps were consistent with the I/R and SI groups. Two hours after ischemia of the right middle cerebral artery, the thread embolism was removed, the blood flow was restored, and the middle cerebral artery was reperfused for 24 hours. According to the Zea longa score, rats with successful modeling were selected. 2, 3, 5-triphenyltetrazolium chloride (TTC) was used to detect the volume of cerebral infarct and the water content of brain tissue was measured by dry/wet weight method. The permeability of BBB was detected by the Evans blue (EB) tracer method. The matrix metalloproteinase(MMP-9) and tissue inhibitor of metalloproteinase-1(TIMP-1)protein expressions were determined with Western blot. The measured data of the three groups of rats were compared, and the influence of SI pretreatment on the above observations was analyzed.Results The neurological function score, cerebral infarction volume, the content of water and EB of brain tissue in SI group and I/R group were higher than those in Sham group, while SI group was lower than I/R group[(1.50±1.13),(2.33±0.82)and (0.00±0.00) scores; 12.5%±2.34%, 37.50%±2.28% and 0.07%±0.03%; 81.75%±0.86%, 84.17%±0.54% and 78.24%±0.41%;(46.50±1.41),(55.44±1.37)and(3.83±1.49)μg /g , respectively]. The differences were statistically significant (all P values<0.01). The expressions of MMP-9 and TIMP-1 in SI group and I/R group were significantly higher than those in Sham group(0.81±0.23, 1.15±0.14, 1.15±0.14 and 2.31±0.20, 1.62±0.21, 1.62±0.21, respectively). The differences were statistically significant (all P values <0.01). Compared with the I/R group, the expression of MMP-9 was decreased and the expression of TIMP-1 was increased in the SI group. The differences were statistically significant (all P values<0.01).Conclusions SI may down-regulate MMP-9 protein expression and up-regulate TIMP-1 protein expression in brain tissue after ischemia-reperfusion, and decrease permeability of BBB and reduces the degree of brain edema and EB content of brain tissue after ischemia-reperfusion.
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