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健脾止动汤对抽动障碍小鼠各脑区Cx43、Cx30的影响

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目的 探究健脾止动汤对抽动障碍小鼠皮质、纹状体、下丘脑及海马中连接蛋白43(Cx43)及连接蛋白30(Cx30)表达的干预作用。方法 60只雄性ICR小鼠按随机数字表法分为空白对照组(15只)和造模组(45只),造模组小鼠腹腔注射亚氨基二丙腈(350 mg/kg,每日1次,连续7 d)建立抽动障碍模型,空白对照组腹腔注射等体积生理盐水。进行刻板行为评分评价造模是否成功,按随机数字表法将造模组小鼠分为模型组、泰必利组(29。5 mg/kg)和健脾止动汤组(17。8g/kg),每组15只。灌胃给药4周。给药结束后,进行刻板行为评分,采用免疫组织化学法、蛋白质印迹法、实时荧光PCR法分别检测皮质、纹状体、下丘脑及海马中Cx43、Cx30蛋白阳性表达、蛋白表达及mRNA表达。结果 与空白对照组比较,模型组小鼠刻板行为评分增加(P<0。05);与模型组比较,泰必利组、健脾止动汤组小鼠刻板行为评分降低(P<0。05)。与空白对照组比较,模型组小鼠皮质、纹状体、下丘脑、海马Cx43平均光密度值降低(P<0。05);与模型组比较,泰必利组皮质、海马Cx43平均光密度值升高,健脾止动汤组皮质、纹状体、海马Cx43平均光密度值升高(P<0。05);与泰必利组比较,健脾止动汤组皮质Cx43平均光密度值升高(P<0。05)。与空白对照组比较,模型组小鼠皮质、纹状体、下丘脑、海马Cx30平均光密度值降低(P<0。05);与模型组比较,泰必利组纹状体、下丘脑Cx30平均光密度值升高,健脾止动汤组皮质、纹状体、海马Cx30平均光密度值升高(P<0。05);与泰必利组比较,健脾止动汤组海马Cx30平均光密度值升高(P<0。05)。与空白对照组比较,模型组小鼠皮质、纹状体、海马Cx43蛋白表达降低(P<0。05);与模型组比较,泰必利组皮质Cx43蛋白表达升高,健脾止动汤组皮质、纹状体、海马Cx43蛋白表达升高(P<0。05)。与空白对照组比较,模型组小鼠皮质、海马Cx30蛋白表达降低(P<0。05);与模型组比较,泰必利组和健脾止动汤组皮质、海马Cx30蛋白表达均升高(P<0。05)。与空白对照组比较,模型组皮质、纹状体、海马Cx43 mRNA表达下降(P<0。05);与模型组比较,泰必利组和健脾止动汤组皮质、纹状体、海马Cx43 mRNA表达均升高(P<0。05)。与空白对照组比较,模型组皮质、海马Cx30 mRNA表达下降(P<0。01);与模型组比较,泰必利组和健脾止动汤组皮质、海马Cx30 mRNA表达均升高(P<0。05)。结论 皮质、纹状体、下丘脑及海马Cx43、Cx30表达降低可能参与抽动障碍小鼠刻板行为发生,健脾止动汤的干预机制可能与增加各脑区Cx43、Cx30表达有关。
Effects of Jianpi Zhidong Decoction on Cx43 and Cx30 in brain regions of tic disorder mice
Objective To study the intervention effect of Jianpi Zhidong Decoction on the expressions of Cx43 and Cx30 in the cortex,corpus striatum,hypothalamus,and hippocampus of tic disorder mice.Methods According to the random number table method,60 male ICR mice were divided into the blank control group(n=15)and modeling group(n=45).The mice in the modeling group were intraperitoneally injected with iminodipropanitrile(350 mg/kg,once a day for 7 days)to establish a tic disorder model,and the mice in the blank control group were intraperitoneally injected with equal volume of normal saline.The stereotyped behavior score was calculated to evaluate the success of modeling.According to the random number table method,the mice in the modeling group were divided into the model group,tiapride group(29.5 mg/kg)and Jianpi Zhidong Decoction group(17.8 g/kg),with 15 mice in each group.The drug was administered by gavage for 4 weeks.After administration,stereotyped behavior score was calculated.The positive protein expression,protein expression,and mRNA expression of Cx43 and Cx30 in the cortex,corpus striatum,hypothalamus and hippocampus were determined by immunohistochemistry,Western blotting and real-time PCR.Results Compared with the blank control group,the stereotyped behavior score of mice in the model group was increased(P<0.05).Compared with the model group,the stereotyped behavior scores of mice in the tiapride group and the Jianpi Zhidong Decoction group were decreased(P<0.05).Compared with the blank control group,the average optical densities of Cx43 in the cortex,corpus striatum,hypothalamus,and hippocampus of mice in model group were decreased(P<0.05).Compared with the model group,the average optical densities of Cx43 in the cortex and hippocampus in the tiapride group were increased,and the average optical densities of Cx43 in the cortex,corpus striatum,and hippocampus in the Jianpi Zhidong Decoction group were increased(P<0.05).Compared with the tiapride group,the average optical density of Cx43 in the cortex in the Jianpi Zhidong Decoction group was increased(P<0.05).Compared with the blank control group,the average optical densities of Cx30 in the cortex,corpus striatum,hypothalamus,and hippocampus of mice in model group were decreased(P<0.05).Compared with the model group,the average optical densities of Cx30 in the corpus striatum and hypothalamus in the tiapride group were increased,and the average optical densities of Cx30 in the cortex,corpus striatum,and hippocampus in the Jianpi Zhidong Decoction group were increased(P<0.05).Compared with the tiapride group,the average optical density of Cx30 in the hippocampus in the Jianpi Zhidong Decoction group was increased(P<0.05).Compared with the blank control group,the protein expressions of Cx43 in the cortex,corpus striatum,and hippocampus of mice in the model group were decreased(P<0.05).Compared with the model group,the protein expression of Cx43 in the cortex in the tiapride group was increased,and the protein expressions of Cx43 in the cortex,corpus striatum,and hippocampus in the Jianpi Zhidong Decoction group were increased(P<0.05).Compared with the blank control group,the protein expressions of Cx30 in the cortex and hippocampus of mice in the model group were decreased(P<0.05).Compared with the model group,the protein expressions of Cx30 in the cortex and hippocampus in the tiapride group and the Jianpi Zhidong Decoction group were increased(P<0.05).Compared with the blank control group,the mRNA expressions of Cx43 in the cortex,corpus striatum and hippocampus in the model group were decreased(P<0.05).Compared with the model group,the mRNA expressions of Cx43 in the cortex,corpus striatum,and hippocampus in the tiapride group and the Jianpi Zhidong Decoction group were increased(P<0.05).Compared with the blank control group,the mRNA expressions of Cx30 in the cortex and hippocampus in the model group were decreased(P<0.01).Compared with the model group,the mRNA expressions of Cx30 in the cortex and hippocampus in the tiapride group and the Jianpi Zhidong Decoction group were increased(P<0.05).Conclusion The decreased expression of Cx43 and Cx30 in the cortex,corpus striatum,hypothalamus,and hippocampus may be involved in the occurrence of stereotyped behavior in tic disorder mice.The intervention mechanism of Jianpi Zhidong Decoction may be related to the increased expression of Cx43 and Cx30 in various brain regions.

Jianpi Zhidong Decoctiontic disorderCx43Cx30spleen governing musclemice

黄家伟、郝宏文、杨宗贤、赵荣华、王道涵

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北京中医药大学 北京 100029

北京中医药大学东方医院

中国中医科学院中药研究所

健脾止动汤 抽动障碍 连接蛋白43 连接蛋白30 脾主肌肉 小鼠

国家自然科学基金青年科学基金项目

81403431

2024

北京中医药大学学报
北京中医药大学

北京中医药大学学报

CSTPCD北大核心
影响因子:1.568
ISSN:1006-2157
年,卷(期):2024.47(1)
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