天舒胶囊对偏头痛大鼠TCC内PPARs调控的研究

发布时间：2018-08-07 16:44

【摘要】：偏头痛(migraine)是一种常见的神经系统疾病,因其发病率高,反复发作,发作时疼痛剧烈,迁延难愈等特点,给患者造成极大的痛苦,并且与脑梗死、抑郁症等多种疾病密切相关,严重影响着人类的健康。因此,偏头痛的防治是医学研究的重要课题。中医药从整体观念出发进行辨证论治,治疗偏头痛具有自身的优势与特点。然而由于基础研究相对薄弱,限制了中医药防治偏头痛优势的发挥,因此将传统中医学理论与现代医学前沿相结合,进一步研究中医药防治偏头痛的深层机制,为中医药防治偏头痛提供新的证据支持,对中医药更好地发展与更广泛的传播具有重要意义。研究目的:1.探索偏头痛大鼠不同时间节点三叉神经颈复合体(trigeminal cervical complex,TCC)内PPARs各亚型的表达情况,分析PPARs各亚型表达的相对高峰时间。2.研究中成药天舒胶囊对偏头痛大鼠TCC内PPARs各亚型表达的影响,比较天舒胶囊和PPARs激动剂(GW0742)干预后大鼠血浆中CGRP的变化,进一步阐述天舒胶囊治疗偏头痛的作用机制。研究方法:实验一不同时间节点偏头痛大鼠TCC内PPARs各亚型的表达1.24只SD大鼠分为模型组和空白组,空白组正常饲养,模型组给予皮下注射硝酸甘油的方法造模。2.造模后持续录像2小时,观察大鼠行为学变化。3.造模后2小时空白组和模型组各取6只大鼠,麻醉后断头取脑组织,造模后4小时,同样方法取剩余大鼠脑组织。4.免疫组化法观察PPARs各亚型在TCC中的表达。实验二天舒胶囊对PPARs各亚型表达的调控研究1.32只大鼠分为4组,空白组(正常饲养,不给任何处理),模型组(生理盐水灌胃7天后,给予造模),天舒胶囊组(天舒胶囊水溶液灌胃7天后,给予造模),GW0742组(生理盐水灌胃7天后,腹腔注射GW0742,半小时后给予造模)。2.造模后给予录像2小时观察行为学变化。3.造模后4小时腹主动脉取血,断头取脑组织。4.ELISA法检测血浆中CGRP含量,免疫组化法检测PPARs各亚型在TCC中的表达。研究结果:1.PPARα在偏头痛大鼠TCC内表达趋势是先降低后升高;PPARβ在偏头痛大鼠TCC中的表达趋势在4小时内持续升高;PPARy在偏头痛大鼠TCC中的表达趋势是先升高后回降至正常。2.天舒胶囊和GW0742均可以降低偏头痛大鼠的行为学评分,进而用来治疗偏头痛。3.天舒胶囊可以增加PPARα、PPARβ在偏头痛大鼠TCC中的表达,而对PPARγ的表达无影响;GW0742可以增加PPARβ在TCC中的表达,抑制PPARα的表达,对PPARγ表达无影响。4.天舒胶囊和GW0742均可以降低偏头痛模型大鼠血浆中CGRP的水平。结论意义:1.天舒胶囊对防止偏头痛的发生有一定的积极作用。2.天舒胶囊可以通过激活偏头痛大鼠模型TCC内PPARα、PPARβ的表达以及降低血浆中CGRP的水平来达到防止偏头痛发生的目的。3.天舒胶囊有类似于PPAR β激动剂的效果来激活PPARβ进而防止偏头痛的发生,但是其作用效果与PPARβ激动剂有所不同。4.PPARs可能是未来中药防治偏头痛的一个新的靶点。
[Abstract]:Migraine (migraine) is a common nervous system disease. Because of its high incidence, recurrent attacks, severe pain and difficult to recover, it causes great pain and is closely related to many diseases such as cerebral infarction and depression, which seriously affect human health. Therefore, the prevention and control of migraine is important in medical research. Chinese medicine has its own advantages and characteristics in treating migraine from the whole concept. However, because the basic research is relatively weak, it restricts the exertion of the advantage of the prevention of migraine in traditional Chinese medicine. Therefore, the traditional Chinese medicine theory is combined with the frontier of modern medicine to further study the deep level of the prevention of migraine in traditional Chinese medicine. The mechanism provides new evidence support for the prevention and control of migraine in traditional Chinese medicine. It is of great significance to the better development and wider spread of traditional Chinese medicine. 1. to explore the expression of PPARs subtypes in trigeminal cervical complex (TCC) in different time nodes of migraine rats, and to analyze the expression of each subtype of PPARs. The relative peak time.2. study on the effect of Chinese medicine Tianshu Capsule on the expression of PPARs subtypes in TCC of migraine rats, compared the changes of CGRP in the plasma of rats after the intervention of Tianshu capsule and PPARs agonist (GW0742), and further elaborated the mechanism of the action of Tianshu capsule in the treatment of migraine. The research method: the experiment of a different time node migraine rat TC The expression of each subtype of C PPARs in 1.24 SD rats was divided into model group and blank group, the blank group was raised normally, and the model group was given a method of subcutaneous injection of nitroglycerin for 2 hours after making models of the model group and observed the behavior changes of the rats after the.3. model and the 2 hour blank group and the model group. After the anesthesia, the brain tissue was taken out of the head and the model was made after the anesthesia. 4 hours, the same method was used to observe the expression of PPARs subtypes in TCC by using.4. immunohistochemistry in the remaining rat brain tissue. Experimental two Tianshu capsule was used to regulate the expression of PPARs subtypes. 1.32 rats were divided into 4 groups, the blank group (normal feeding, no treatment), the model group (7 days after gavage of raw saline), Tianshu capsule group (day) The water solution of Shu Capsule was given 7 days after gastric perfusion. Group GW0742 (7 days after gastric perfusion, intraperitoneal injection of GW0742, half an hour after being given model),.2. was given a video for 2 hours to observe behavioral changes and observe behavioral changes in the abdominal aorta for 4 hours after 2 hours. The content of CGRP in plasma was detected by.4.ELISA method of brain tissue, and PPARs was detected by immunohistochemical method for PPARs. The expression of each subtype in TCC: the expression trend of 1.PPAR alpha in migraine rats was first decreased and then increased; the expression trend of PPAR beta in TCC of migraine rats increased continuously in 4 hours, and the expression trend of PPARy in TCC in migraine rats was first increased and then descended to normal.2. Tianshu capsule and GW0742 to reduce the bias. The behavior score of the pain rats, and then used to treat migraine.3. Tianshu capsule can increase the expression of PPAR a, PPAR beta in the TCC of migraine rats, but no influence on the expression of PPAR gamma; GW0742 can increase the expression of PPAR beta in TCC, inhibit the expression of PPAR alpha, and do not affect the expression of.4. Tianshu capsule and GW0742 to reduce migraine. The level of CGRP in plasma of rat model. Conclusion: 1. Tianshu capsule has a positive effect on preventing migraine..2. Tianshu capsule can be activated by activating PPAR alpha in TCC of migraine rat model, expression of PPAR beta and reducing the level of CGRP in plasma to prevent migraine from occurrence of migraine,.3. Tianshu capsule is similar to PPAR The effect of beta agonist activates PPAR beta and then prevents migraine, but its effect is different from that of PPAR beta agonist,.4.PPARs may be a new target for the prevention and treatment of migraine in the future.
【学位授予单位】：北京中医药大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R285.5

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