本文選題：連夏配方顆粒 + NGF/TrKA/SH2B�。� 參考：《北京中醫(yī)藥大學(xué)》2015年博士論文

【摘要】：心肌梗死發(fā)生后,心肌梗死周邊區(qū)的交感神經(jīng)與迷走神經(jīng)均會(huì)發(fā)生神經(jīng)重構(gòu)。而由此引發(fā)心電生理以及復(fù)極離散系列性、繼發(fā)性的紊亂成為心肌梗死后致命性心律失常發(fā)生的關(guān)鍵性因素。而心肌梗死周圍區(qū)則是心肌梗死發(fā)生后心肌組織修復(fù)、神經(jīng)再生的活躍區(qū)域,與心肌梗死中心區(qū)域和正常區(qū)域相比更加顯著。找到有效地解決心肌梗死后心臟自主神經(jīng)重構(gòu)的辦法迫在眉睫。本論文將從文獻(xiàn)綜述、系統(tǒng)評(píng)價(jià)、實(shí)驗(yàn)研究三個(gè)方面對(duì)心肌梗死后心梗周邊區(qū)心臟自主神經(jīng)重構(gòu)進(jìn)行探討,以期發(fā)現(xiàn)連夏配方顆粒在改善心肌梗死后心梗周邊區(qū)心臟自主神經(jīng)重構(gòu)過程中的作用與機(jī)制。第一部分文獻(xiàn)綜述就近年來國(guó)內(nèi)外對(duì)心肌梗死后心臟交感神經(jīng)重構(gòu)與心律失常的關(guān)系、神經(jīng)生長(zhǎng)因子與心血管疾病的相關(guān)性以及神經(jīng)生長(zhǎng)因子受體生理功能及其信號(hào)轉(zhuǎn)導(dǎo)等研究進(jìn)展進(jìn)行了詳細(xì)綜述,介紹了目前國(guó)內(nèi)外有關(guān)心肌梗死后心臟自主神經(jīng)重構(gòu)研究中的最新理論觀點(diǎn)、工作進(jìn)展情況以及未來研究發(fā)展趨勢(shì)等,并初步討論了目前研究中仍然存在、尚需解決的問題。第二部分系統(tǒng)評(píng)價(jià)目的系統(tǒng)評(píng)價(jià)黃連溫膽湯治療心律失常的療效和安全性。方法全面收集黃連溫膽湯治療心律失常的隨機(jī)對(duì)照試驗(yàn)(randomized controlled trial,RCT),根據(jù)納入標(biāo)準(zhǔn)嚴(yán)格篩選,使用STATA11.0分析軟件進(jìn)行Meta薈萃分析。結(jié)果黃連溫膽湯組可以明顯改善心律失常的各結(jié)局指標(biāo),并且其療效均高于對(duì)照組。二者綜合療效總有效率合并效應(yīng)量為[RR=1.267,95%CI:1.157-1.386, P=0.000]、綜合療效顯效率合并效應(yīng)量為[RR=1.340,95%CI:1.111-1.616, P=0.002]、臨床癥狀總有效率合并效應(yīng)量為[RR=1.238,95%CI:1.015-1.510, P=0.035]、動(dòng)態(tài)心電圖室早總有效率合并效應(yīng)量為[RR=1.256,95%CI:1.003-1.573, P=0.047]。結(jié)論黃連溫膽湯能夠明顯改善心律失常的綜合療效總有效率與顯效率、臨床癥狀總有效率和動(dòng)態(tài)心電圖室早總有效率等相關(guān)指標(biāo),但是由于本次系統(tǒng)評(píng)價(jià)所納入研究的方法質(zhì)量不高和可能存在發(fā)表偏倚等不良因素,本次系統(tǒng)評(píng)價(jià)的結(jié)果與結(jié)論尚需要高質(zhì)量、多中心的隨機(jī)雙盲臨床對(duì)照試驗(yàn)來進(jìn)一步證實(shí)。第三部分實(shí)驗(yàn)研究目的觀察TH、AchE、NGF、TrKA、SH2B、Erkl/2的mRNA與TH、AchE、NGF、 TrKA、p-TrkA、SH2B、Erkl/2、 p-Erkl/2的蛋白表達(dá)水平變化在連夏配方顆粒干預(yù)心肌梗死后心梗周邊區(qū)心臟自主神經(jīng)重構(gòu)中的作用。方法將105只健康雄性清潔級(jí)42-49日齡Wistar大鼠,按照隨機(jī)數(shù)字表法隨機(jī)分為正常組、假手術(shù)組、心梗模型組(模型組)、美托洛爾組(西藥組)、連夏配方顆粒大、中、小劑量(189.00 mg/kg、94.50 mg/kg、47.25 mg/kg)組共計(jì)7個(gè)組,每組大鼠15只。正常組大鼠不做處理,美托洛爾組、中藥大、中、小劑量組大鼠均結(jié)扎左冠狀動(dòng)脈前降支以建立急性心肌梗死大鼠模型,假手術(shù)組大鼠只穿線不結(jié)扎。于模型建立當(dāng)天即開始灌胃,正常組、假手術(shù)與模型組大鼠予生理鹽水灌胃,余各組均予相應(yīng)實(shí)驗(yàn)藥物。連續(xù)灌胃給藥30天后麻醉大鼠,迅速于冰上獲取大鼠心肌梗死周圍區(qū)相同部位處足量心肌組織,Real Time PCR方法檢測(cè)心肌組織中TH、AchE、NGF、TrKA、SH2B、Erkl/2的mRNA表達(dá)水平；Western Blot方法檢測(cè)心肌組織中TH、AchE、NGF、TrKA、p-TrkA、 SH2B、 Erkl/2、p-Erkl/2的蛋白表達(dá)水平。結(jié)果①對(duì)TH mRNA的影響：與正常組、假手術(shù)組比較,模型組大鼠心梗周圍區(qū)心肌組織TH mRNA表達(dá)明顯升高(P0.05)。治療后,與模型組比較,美托洛爾組、連夏配方顆粒189.00、94.50、47.25mg/kg組大鼠心梗周圍區(qū)TH mRNA表達(dá)均明顯降低(P0.05)。與美托洛爾組比較,連夏配方顆粒189.00 mg/kg組大鼠心梗周圍區(qū)THmRNA表達(dá)明顯降低(P0.05)。②對(duì)AchE mRNA的影響：與正常組、假手術(shù)組比較,心梗模型組大鼠心梗周圍區(qū)AchE mRNA表達(dá)顯著升高(P0.01)。治療后,與模型組比較,美托洛爾組大鼠心梗周圍區(qū)AchE mRNA表達(dá)未見明顯降低(P0.05)；連夏配方顆粒189.00、94.50、47.25 mg/kg組大鼠心梗周圍區(qū)AchE mRNA表達(dá)均顯著降低(P0.01)。與美托洛爾組比較,連夏配方顆粒189.00 mg/kg組大鼠心梗周圍區(qū)AchE mRNA表達(dá)顯著降低(P0.01)；連夏配方顆粒94.50 mg/kg組大鼠心梗周圍區(qū)AchE mRNA表達(dá)明顯降低(P0.05)。③對(duì)NGF mRNA的影響：與正常組、假手術(shù)比較,心梗模型組大鼠心梗周圍區(qū)NGF mRNA表達(dá)顯著升高(P0.01)。治療后,與模型組比較,美托洛爾組、連夏配方顆粒189.00、94.50、47.25 mg/kg組大鼠心梗周圍區(qū)NGFmRNA表達(dá)均顯著降低(P0.01)。與美托洛爾組比較,連夏配方顆粒189.00 mg/kg組大鼠心梗周圍區(qū)NGF mRNA表達(dá)明顯降低(P0.05)。④對(duì)TrKA mRNA的影響：與正常組、假手術(shù)組比較,心梗模型組大鼠心梗周圍區(qū)TrKA mRNA表達(dá)顯著升高(P0.01)。治療后,與模型組比較,美托洛爾組、連夏配方顆粒189.00、94.50mg/kg組大鼠心梗周圍區(qū)TrKA mRNA表達(dá)均顯著降低(P0.01)。與美托洛爾組比較,連夏配方顆粒189.00、94.50 mg/kg組大鼠心梗周圍區(qū)TrKA mRNA表達(dá)均未見明顯變化(P0.05)。⑤對(duì)SH2B mRNA的影響：與正常組、假手術(shù)組比較,心梗模型組大鼠心梗周圍區(qū)SH2B mRNA表達(dá)顯著升高(P0.01)。治療后,與模型組比較,美托洛爾組、連夏配方顆粒189.00、94.50、47.25mg/kg組大鼠心梗周圍區(qū)SH2B mRNA表達(dá)均顯著降低(P0.01)。與美托洛爾組比較,連夏配方顆粒189.00 mg/kg 組大鼠心梗周圍區(qū) SH2B mRNA表達(dá)明顯降低(P0.05)。⑥對(duì)Erk1/2 mRNA的影響：與正常組、假手術(shù)組比較,心梗模型組大鼠心梗周圍區(qū)Erk1/2 mRNA表達(dá)顯著升高(P0.01)。治療后,與模型組比較,美托洛爾組、連夏配方顆粒189.00、94.50mg/kg組大鼠心梗周圍區(qū)Erkl/2 mRNA表達(dá)均顯著降低(P0.01)。與美托洛爾組比較,連夏配方顆粒189.00mg/kg組大鼠心梗周圍區(qū)Erk1/2 mRNA表達(dá)顯著降低(P0.01)。⑦對(duì)TH的影響：與正常組、假手術(shù)組比較,模型組大鼠心梗周圍區(qū)TH表達(dá)明顯升高(P0.05)。治療后,與模型組比較,美托洛爾組大鼠心梗周圍區(qū)TH表達(dá)明顯降低(P0.05)；連夏配方顆粒189.00 mg/kg組大鼠心梗周圍區(qū)TH表達(dá)顯著降低(P0.01)。與美托洛爾組比較,連夏配方顆粒189.00 mg/kg組大鼠心梗周圍區(qū)TH表達(dá)無明顯變化(P0.05)。⑧對(duì)AchE的影響：與正常組、假手術(shù)組比較,模型組大鼠心梗周圍區(qū)AchE表達(dá)明顯升高(P0.05)。治療后,與模型組比較,美托洛爾組大鼠心梗周圍區(qū)AchE表達(dá)未見明顯降低(P0.05)；連夏配方顆粒189.00、94.50 mg/kg組大鼠心梗周圍區(qū)AchE表達(dá)均明顯降低(P0.05)。與美托洛爾組比較,連夏配方顆粒189.00 mg/kg組大鼠心梗周圍區(qū)AchE表達(dá)明顯降低(P0.05)。⑨對(duì)NGF的影響：與正常組、假手術(shù)組比較,模型組大鼠心梗周圍區(qū)NGF表達(dá)明顯升高(P0.05)。治療后,與模型組比較,美托洛爾組、連夏配方顆粒189.00 mg/kg組大鼠心梗周圍區(qū)NGF表達(dá)均明顯降低(P0.05)。與美托洛爾組比較,連夏配方顆粒189.00 mg/kg組大鼠心梗周圍區(qū)NGF表達(dá)未見明顯變化(P0.05)。⑩對(duì)TrKA的影響：經(jīng)比較各組大鼠心肌組織TrKA表達(dá)水平的均值發(fā)現(xiàn),模型組大鼠心梗周圍區(qū)TrKA的表達(dá)要高于其余各組。治療后,各治療組大鼠心梗周圍區(qū)TrKA的表達(dá)均低于心梗模型組。11對(duì)p-TrKA的影響：與正常組、假手術(shù)組比較,模型組大鼠心梗周圍區(qū)p-TrKA表達(dá)均顯著升高(P0.01)。治療后,與模型組比較,美托洛爾組、連夏配方顆粒189.00、94.50 mg/kg組大鼠心梗周圍區(qū)p-TrKA表達(dá)均顯著降低(P0.01)。與美托洛爾組比較,連夏配方顆粒189.00 mg/kg組大鼠心梗周圍區(qū)p-TrKA顯著降低(P0.01)。⑩對(duì)SH2B的影響：與假手術(shù)組比較,模型組大鼠心梗周圍區(qū)SH2B表達(dá)明顯升高(P0.05)。治療后,與模型組比較,美托洛爾組、連夏配方顆粒94.50 mg/kg組大鼠心梗周圍區(qū)SH2B表達(dá)均明顯降低(P0.05)。與美托洛爾組比較,連夏配方顆粒94.50 mg/kg組大鼠心梗周圍區(qū)SH2B均未見明顯變化(P0.05)。⑩對(duì)Erk1/2的影響：與正常組、假手術(shù)組比較,模型組大鼠心梗周圍區(qū)Erk1/2表達(dá)明顯升高(P0.05)。治療后,與模型組比較,美托洛爾組、連夏配方顆粒94.50、47.25 mg/kg組大鼠心梗周圍區(qū)Erk1/2表達(dá)均明顯降低(P0.05)。與美托洛爾組比較,連夏配方顆粒94.50、47.25 mg/kg組大鼠心梗周圍區(qū)Erk1/2表達(dá)均未見明顯變化(P0.05)。14對(duì)p-Erk1/2的影響：與正常組、假手術(shù)組比較,模型組大鼠心梗周圍區(qū)p-Erkl/2表達(dá)明顯升高(P0.05)。治療后,與模型組比較,美托洛爾組大鼠心梗周圍區(qū)p-Erkl/2表達(dá)明顯降低(P0.05)；連夏配方顆粒47.25 mg/kg組大鼠心梗周圍區(qū)p-Erkl/2表達(dá)顯著降低(P0.01)。與美托洛爾組比較,連夏配方顆粒47.25 mg/kg組大鼠心梗周圍區(qū)p-Erkl/2表達(dá)均未見明顯變化(P0.05)結(jié)論：①冠脈結(jié)扎法心肌梗死模型大鼠心梗周邊區(qū)TH、AchE表達(dá)升高,出現(xiàn)了心臟交感神經(jīng)和迷走神經(jīng)的新生和再分布,是研究心梗后心梗周邊區(qū)心臟自主神經(jīng)重構(gòu)的理想動(dòng)物模型。②美托洛爾可以抑制心梗后心梗周邊區(qū)交感神經(jīng)重構(gòu),但對(duì)心梗后心梗周邊區(qū)迷走神經(jīng)重構(gòu)的作用效果不明顯；連夏配方顆粒既可以抑制心梗后心梗周邊區(qū)交感神經(jīng)重構(gòu),又可以抑制心梗后心梗周邊區(qū)迷走神經(jīng)重構(gòu)。③心梗后大鼠心梗周邊區(qū)NGF水平升高、TrKA表達(dá)增加,SH2B表達(dá)上調(diào),進(jìn)而上調(diào)Erkl/2表達(dá),引起TH、AchE合成增加,促進(jìn)了交感神經(jīng)和迷走神經(jīng)的新生和再分布,漸至自主神經(jīng)重構(gòu)。這可能是心梗后心梗周邊區(qū)心臟自主神經(jīng)重構(gòu)發(fā)生機(jī)制之一。④連夏配方顆粒可以通過降低心梗后心梗周邊區(qū)NGF水平,降低TrKA、SH2B表達(dá),進(jìn)而下調(diào)Erkl/2表達(dá),即下調(diào)NGF介導(dǎo)的TrKA信號(hào)通路的關(guān)鍵信號(hào)靶點(diǎn)的表達(dá),限制TH、AchE合成,減弱心梗周邊區(qū)交感神經(jīng)和迷走神經(jīng)的新生和再分布,抑制心臟自主神經(jīng)重構(gòu)。
[Abstract]:After the onset of myocardial infarction, the sympathetic and vagus nerve in the surrounding area of the myocardial infarction will have neural remodeling, which leads to electrocardio physiology and the discrete seriation of repolarization. Secondary disorder becomes the key factor for the occurrence of fatal arrhythmia after myocardial infarction, and the surrounding area of myocardial infarction is the myocardial group after the onset of myocardial infarction. It is imminent to find an effective way to solve the cardiac autonomic nerve reconstruction after myocardial infarction. This paper will discuss three aspects of the cardiac autonomic nerve in the peripheral area of myocardial infarction after myocardial infarction, from the literature review, systematic evaluation and experimental study. The role and mechanism of Lian Xia formula granules in improving cardiac autonomic nerve reconstruction in the peripheral region of myocardial infarction after myocardial infarction were explored in order to find out the relationship between cardiac sympathetic remodeling and arrhythmia after myocardial infarction, and the correlation between nerve growth factor and cardiovascular disease in recent years. The research progress of the physiological function and signal transduction of the nerve growth factor receptor is reviewed in detail. The latest theoretical views, work progress and future research trends in the study of cardiac autonomic nerve reconstruction after myocardial infarction are introduced, and the current research is still discussed. The second part of the system evaluation is to evaluate the efficacy and safety of Huanglian Wendan Decoction in the treatment of arrhythmia. Methods a randomized controlled trial (randomized controlled trial, RCT) of Huanglian Wendan Decoction (Huanglian Wendan Decoction) was collected for the treatment of arrhythmia. According to the standard strict screening, STATA11.0 analysis software was used to carry out Meta meta-analysis. Results Huanglian Wendan Decoction group can obviously improve the outcome indexes of arrhythmia, and its curative effect is higher than that of the control group. The total effective rate of combined effect is [RR=1.267,95%CI:1.157-1.386, P=0.000], the combined effect of comprehensive effect is [RR= 1.340,95%CI:1.111-1.616, P=0.002], and the clinical symptoms are all effective. The rate of rate of combined effect was [RR=1.238,95%CI:1.015-1.510, P=0.035], the early total effective rate of combined effect was [RR=1.256,95%CI:1.003-1.573 in dynamic electrocardiogram room. Conclusion Huanglian Wendan Decoction can obviously improve the total effective efficiency and effective efficiency of the comprehensive curative effect of arrhythmia, the total effective rate of clinical symptoms and the early total effective rate of the dynamic electrocardiogram room. The results and conclusions of this system evaluation still need high quality, and the results and conclusions of this system still need high quality, and the multi center randomized double blind clinical trial to further confirm. The third part of the experimental study aims to observe TH, AchE, NGF, TrKA, SH2B, The protein expression of Erkl/2 mRNA and TH, AchE, NGF, TrKA, p-TrkA, SH2B, Erkl/2, p-Erkl/2 changes in the intervention of cardiac autonomic nerve reconstruction in the periphery of myocardial infarction after myocardial infarction by Lian Xia formula granules. Methods 105 healthy male clean grade 42-49 day old rats were randomly divided into normal group and sham operation according to random number table method. Group, myocardial infarction model group (model group), metoprolol group (Western medicine group), Lian Xia formula granule large, medium and small dose (189 mg/kg, 94.50 mg/kg, 47.25 mg/kg) group total 7 groups, each group of 15 rats. Normal group rats do not do treatment, metoprolol group, large, medium, small dose group of rats were ligated to the left anterior descending coronary artery to establish acute myocardial infarction Rats in the sham operation group were only dressed in the sham operation group without ligature. The normal group, the normal group, the sham operation and the model group were given the normal saline, and the other groups were given the corresponding experimental drugs. After 30 days of continuous perfusion, the rats were anesthetized, and the full amount of myocardium around the same area around the infarct area of the rat was quickly obtained on the ice. The expression level of TH, AchE, NGF, TrKA, SH2B, Erkl/2 in myocardial tissue was detected by Real Time PCR method. The expression of TH mRNA in myocardial tissue was significantly increased (P0.05). After treatment, the expression of TH mRNA in the peripheral zone of myocardial infarction in the group of metoprolol and the group 189.00,94.50,47.25mg/kg of Lian Xia formula was significantly decreased (P0.05). Compared with the metoprolol group, the expression of THmRNA in the area around myocardial infarction in the 189 mg/kg group of Lian Xia formula granule was significantly reduced (P0.0). 5). The effect on AchE mRNA: compared with the normal group and the sham operation group, the expression of AchE mRNA in the myocardial infarction group was significantly increased (P0.01). Compared with the model group, the expression of AchE mRNA in the peripheral region of the metoprolol group was not significantly reduced (P0.05), and even the summer formula 189.00,94.50,47.25 mg/kg group rat myocardial infarction. The expression of AchE mRNA in the surrounding area was significantly decreased (P0.01). Compared with the metoprolol group, the expression of AchE mRNA in the area around myocardial infarction in the 189 mg/kg group was significantly lower (P0.01), and the expression of AchE mRNA expression in the area around myocardial infarction in the 94.50 mg/kg group of Lian Xia formula granule significantly decreased (P0.05). Compared with the myocardial infarction model group, the expression of NGF mRNA in the surrounding area of myocardial infarction was significantly increased (P0.01). After treatment, the expression of NGFmRNA in the group of metoprolol group and the group 189.00,94.50,47.25 mg/kg of Lian Xia formula group was significantly decreased (P0.01). Compared with the metoprolol group, the 189 mg/kg group of Lian Xia formula granule was the group of myocardial infarction week. The expression of NGF mRNA in the peri area was significantly reduced (P0.05). (4) the effect on TrKA mRNA: compared with the normal group and sham operation group, the expression of TrKA mRNA in the myocardial infarction group was significantly increased (P0.01). After treatment, the expression of TrKA mRNA in the metoprolol group and the group 189.00,94.50mg/kg group of Lian Xia formula granules was significant. Lower (P0.01). Compared with the metoprolol group, there was no significant change in the expression of TrKA mRNA in the zone of myocardial infarction in the group 189.00,94.50 mg/kg group of Lian Xia formula group (P0.05). 5. The effect on SH2B mRNA: compared with the normal group and the sham group, the expression of SH2B mRNA expression in the myocardial infarction group was significantly higher (P0.01). After treatment, the ratio of SH2B mRNA to the model group was compared with the model group. Compared with metoprolol group, the expression of SH2B mRNA in the area around myocardial infarction in group 189.00,94.50,47.25mg/kg rats was significantly decreased (P0.01). Compared with metoprolol group, the expression of SH2B mRNA in the area around myocardial infarction of Lian Xia formula 189 mg/kg group was significantly lower (P0.05). 6. The effect of 6 on Erk1/2 mRNA was compared with the normal group and the sham operation group. The expression of Erk1/2 mRNA in the myocardial infarction area of myocardial infarction model group increased significantly (P0.01). After treatment, the expression of Erkl/2 mRNA in the peripheral region of the myocardial infarction group was significantly decreased (P0.01) in the metoprolol group and in the group 189.00,94.50mg/kg of Lian Xia formula granule group (P0.01). The expression of 1/2 mRNA was significantly decreased (P0.01). The effect of TH on TH in the model group was significantly higher than that in the normal group and the sham operation group (P0.05). After treatment, the expression of TH in the peripheral region of the metoprolol group was significantly reduced (P0.05), and the TH table in the 189 mg/kg group of rat myocardial infarction around the summer formula granule group was compared with the model group. Compared with metoprolol group, there was no obvious change in TH expression in the surrounding area of myocardial infarction in group 189 mg/kg of Lian Xia formula group (P0.05). The effect of TH on AchE: compared with the normal group and sham operation group, the expression of AchE in the peripheral region of the model group was significantly increased (P0.05). After treatment, the rats of the model group, the rats of the metoprolol group, were compared with the model group. The expression of AchE in the surrounding area of myocardial infarction was not significantly decreased (P0.05), and the expression of AchE in the area around myocardial infarction in group 189.00,94.50 mg/kg was significantly lower (P0.05). Compared with the metoprolol group, the expression of AchE in the 189 mg/kg group of Lian Xia formula granule group was significantly lower (P0.05). The effect on NGF was in the normal group and the sham operation. Compared with the model group, the expression of NGF in the surrounding area of myocardial infarction was significantly increased (P0.05). Compared with the model group, the expression of NGF in the group of 189 mg/kg rats was significantly lower than that in the model group (P0.05). Compared with the metoprolol group, the expression of NGF in the 189 mg/kg group of Lian Xia formula granule group was not clear. The effect of explicit change (P0.05) on TrKA: the expression of TrKA expression in myocardial tissue of rats in each group was compared. The expression of TrKA in the surrounding area of myocardial infarction in the model group was higher than that of the rest. The expression of TrKA in the peripheral area around the myocardial infarction group was lower than the effect of.11 on p-TrKA in the myocardial infarction group: with the normal group and the sham operation group. Compared with the model group, the expression of p-TrKA in the surrounding area of myocardial infarction was significantly increased (P0.01). After treatment, the expression of p-TrKA in the group of 189.00,94.50 mg/kg rats was significantly decreased (P0.01) in the metoprolol group and in the group 189.00,94.50 mg/kg of Lian Xia formula. Compared with the metoprolol group, Lian Xia formula granule group of 189 mg/kg group of rat heart area p-TrKA The effect on SH2B was significantly reduced (P0.01). Compared with the sham group, the expression of SH2B in the surrounding area of the model group was significantly increased (P0.05). After treatment, the expression of SH2B in the group of metoprolol and the group 94.50 mg/kg of Lian Xia formula group was significantly decreased (P0.05). Compared with the metoprolol group, even the summer formula granule was 9. In 4.50 mg/kg group, there was no significant change in SH2B in the peripheral region of myocardial infarction (P0.05). Compared with the normal group and the sham group, the Erk1/2 expression in the peripheral region of the model group was significantly increased (P0.05). After treatment, the model group, the metoprolol group, the 94.50,47.25 mg/kg group in the group 94.50,47.25 mg/kg group, the Erk1/2 table in the surrounding area of the myocardial infarction group. Compared with the metoprolol group, there was no significant change in the expression of Erk1/2 in the peripheral zone of myocardial infarction (P0.05).14 in the group 94.50,47.25 mg/kg group of Lian Xia formula group (P0.05). Compared with the normal group and the sham group, the expression of p-Erkl/2 in the model group was significantly higher than that in the sham group (P0.05). After treatment, the ratio of the p-Erkl/2 to the model group was compared with the model group. Compared with the metoprolol group, the expression of p-Erkl/2 in the surrounding area of myocardial infarction decreased significantly (P0.05), and the expression of p-Erkl/2 in the area around myocardial infarction in the 47.25 mg/kg group was significantly lower (P0.01). Compared with the metoprolol group, there was no significant change in the expression of p-Erkl/2 in the surrounding area of the 47.25 mg/kg group of Lian Xia formula granule (P0.05): (P0.05) conclusion: 1. The expression of TH and AchE in the peripheral area of myocardial infarction in the rat model of myocardial infarction was elevated, and the new and redistribution of the sympathetic and vagus nerves appeared. It was an ideal animal model to study the reconstruction of autonomic nerve in the periphery of myocardial infarction after myocardial infarction. The effect of vagus nerve reconstruction in the peripheral region of myocardial infarction was not obvious. Even the summer formula could inhibit the sympathetic remodeling in the peripheral region of myocardial infarction and the reconstruction of vagus nerve in the peripheral region of myocardial infarction after myocardial infarction. (3) the level of NGF in the peripheral area of myocardial infarction in the rats after myocardial infarction increased, the expression of TrKA was increased, the expression of SH2B was up-regulated, and then the Erkl/2 table was up-regulated. TH, AchE synthesis increase, promote the regeneration and redistribution of sympathetic and vagus nerve, gradually to autonomic nerve reconstruction. This may be one of the mechanisms of cardiac autonomic remodeling in the peripheral area of myocardial infarction after myocardial infarction. (4) Lian Xia formula granule can reduce the level of NGF in the peripheral region of myocardial infarction after myocardial infarction, reduce TrKA, SH2B expression and down regulation. Erkl/2 expression, that is, downregulates the expression of key signal targets of the TrKA signaling pathway mediated by NGF, restraining TH, AchE synthesis, reducing the regeneration and redistribution of sympathetic and vagus nerve in the peripheral region of the myocardial infarction, and inhibiting the reconstruction of cardiac autonomic nerve.
【學(xué)位授予單位】：北京中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2015
【分類號(hào)】：R285.5

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