Effect of baicalin on ATPase and LDH and its regulatory effect on the AC/cAMP/PKA signaling pathway in rats with attention deficit hyperactivity disorder
ZHOU Rong-Yi, WANG Jiao-Jiao, YOU Yue, SUN Ji-Chao, SONG Yu-Chen, YUAN Hai-Xia, HAN Xin-Min
Institute of Pediatrics, Nanjing University of Chinese Medicine/Jiangsu Key Laboratory of Pediatric Respiratory Disease, Nanjing 210023, China
摘要 目的 研究黄芩苷对注意缺陷多动障碍(ADHD)模型大鼠脑突触体腺苷三磷酸(ATP)酶、乳酸脱氢酶(LDH)的影响及对腺苷酸环化酶(AC)/环磷酸腺苷(cAMP)/蛋白激酶A(PKA)信号通路的调控作用。方法 将40只SHR大鼠随机分为模型组、盐酸哌甲酯组(0.07 mg/mL)、黄芩苷低(3.33 mg/mL)、中(6.67 mg/mL)、高剂量组(10 mg/mL),每组8只,另设WKY大鼠8只为正常对照组。Percoll密度梯度离心法制备脑突触体,电镜观察突触体结构;运用比色法检测突触体ATP酶、LDH活性;运用ELISA法检测突触体内AC、cAMP、PKA的含量。结果 与正常对照组比较,模型组大鼠脑突触体存在ATP酶活性降低、LDH活性升高及AC、cAMP、PKA含量降低的改变(P P P P P P P P 结论 盐酸哌甲酯及黄芩苷均能改善ADHD模型大鼠脑突触体ATP酶、LDH活性;黄芩苷的作用与剂量存在相关性,且高剂量黄芩苷较盐酸哌甲酯效果更为显著;黄芩苷可能是通过上调AC/cAMP/PKA信号通路发挥治疗作用。
Abstract:Objective To study the effect of baicalin on synaptosomal adenosine triphosphatase (ATPase) and lactate dehydrogenase (LDH) and its regulatory effect on the adenylate cyclase (AC) /cyclic adenosine monophosphate (cAMP) /protein kinase A (PKA) signaling pathway in rats with attention deficit hyperactivity disorder (ADHD). Methods A total of 40 SHR rats were randomly divided into five groups:ADHD model, methylphenidate hydrochloride treatment (0.07 mg/mL), and low-dose (3.33 mg/mL), medium-dose (6.67 mg/mL), and high-dose (10 mg/mL) baicalin treatment (n=8 each). Eight WKY rats were selected as normal control group. Percoll density gradient centrifugation was used to prepare brain synaptosomes and an electron microscope was used to observe their structure. Colorimetry was used to measure the activities of ATPase and LDH in synaptosomes. ELISA was used to measure the content of AC, cAMP, and PKA. Results Compared with the normal control group, the ADHD model group had a significant reduction in the ATPase activity, a significant increase in the LDH activity, and significant reductions in the content of AC, cAMP, and PKA (P P P P P P P P P Conclusions Both methylphenidate hydrochloride and baicalin can improve synaptosomal ATPase and LDH activities in rats with ADHD. The effect of baicalin is dose-dependent, and high-dose baicalin has a significantly greater effect than methylphenidate hydrochloride. Baicalin exerts its therapeutic effect possibly by upregulating the AC/cAMP/PKA signaling pathway.
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