黄芩苷对注意缺陷多动障碍动物模型生长状态的影响及对CaMKⅡ,ERK1/2的调控作用

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该研究观察黄芩苷对注意缺陷多动障碍动物模型生长状态的影响及对Ca MKⅡ,ERK1/2的调控作用.40只SHR大鼠,随机分为模型组、盐酸哌甲酯组及黄芩苷低、中、高剂量组,每组8只,WKY大鼠8只另设为正常对照组.盐酸哌甲酯组(0.07 g·L-1)及黄芩苷低(3.33 g·L-1)、中(6.67 g·L-1)、高(10 g·L-1)剂量组分别按体质量0.015 m L·g-1灌胃给药,正常组及模型组按体质量灌胃生理盐水.各组大鼠连续灌胃4周,每日2次.每日称取大鼠体质量及剩余饲料量,每周进行统计评估大鼠生长状态.Percoll密度梯度离心法制备脑突触体,电镜观察突触体结构;运用Western blot及Real-time PCR法分别检测突触体内Ca MKⅡ,ERK1/2蛋白及mRNA表达水平.研究结果显示,黄芩苷不影响大鼠的正常进食及体质量增长,甚至较正常组大鼠体质量增长更为显著(P<0.05).在对大鼠突触体内Ca MKⅡ及ERK1/2蛋白表达的影响研究中,各给药组对2种蛋白的表达均较模型组有所增高(P<0.05),且盐酸哌甲酯组及黄芩苷高剂量组Ca MKⅡ及ERK1/2蛋白表达显著升高(P<0.05).通过运用PCR法检测突触体内Ca MKⅡ及ERK1/2 mRNA相对表达量,黄芩苷中、高剂量组及盐酸哌甲酯组显著提高了SHR大鼠突触体内Ca MKⅡ及ERK1/2 mRNA相对表达量(P<0.05).该研究表明,黄芩苷不影响SHR大鼠的正常生长发育,给药安全.黄芩苷及盐酸哌甲酯均能上调Ca MKⅡ及ERK1/2 mRNA及蛋白的相对表达量,黄芩苷的药效稳定性具有一定浓度依赖性.“,”The aim of this study was to observe the effect of baicalin on the growth state of attention deficit hyperactivity disorder animal model and its regulation on Ca MKⅡand ERK1/2.In the present study, a total of 40 SHR rats were randomly divided into model group, methylphenidate hydrochloride group, and low, medium, and high dose baicalin groups, with 8 rats in each group.Eight WKYrats were selected as a normal control group.The methylphenidate hydrochloride group (0.07 g·L-1) and the low (3.33 g·L-1), medium (6.67 g·L-1), and high dose (10 g·L-1) baicalin groups received corresponding drugs by gavage administration according to the body weight (0.015 m L·g-1), while the normal group and the model group received the same volume of normal saline by gavage.Thegavage administration lasted for 4 weeks, twice a day.The body weight of the rats and the amount of remaining feed were weighed daily, and the growth state of the rats was statistically evaluated weekly.Percoll density gradient centrifugation was used to prepare brain synaptosomes and an electron microscope was used to observe their structures.The Ca MKⅡand ERK1/2 protein and mRNA expression levels were detected with Western blot and Real-time PCR methods, respectively.Results showed that baicalin did not affect the normal eating and weight gain of rats, and the weight gain of rats was even more significant than that in the normal group (P<0.05).In the study of its effects on Ca MKⅡand ERK1/2 protein expression in rat synaptosomes, the expression of both proteins in each drug-administered group was higher than that in the model group (P<0.05);besides, the expression levels of Ca MKⅡand ERK1/2 protein were significantly increased in both baicalin high dose group and the methylphenidate hydrochloride group (P<0.05).The relative expression of Ca MKⅡand ERK1/2 mRNA in synaptosome was detected by PCR.The results showed that medium and high doses of baicalin and methylphenidate hydrochloride significantly increased the relative expression of Ca MKⅡand ERK1/2 mRNA in synaptosomes of SHR rats (P<0.05).In conclusion, baicalin does not affect the normal growth and development of SHR rats, so it is safe for administration.Both baicalin and methylphenidate hydrochloride could up-regulate the relative expression of Ca MKⅡand ERK1/2 in mRNA and protein, and the pharmacodynamic stability of baicalin is in a dose-dependent manner to certain extent.
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