本文選題：電針 + 肝葉部分切除術(shù)　； 參考：《西南醫(yī)科大學(xué)》2017年碩士論文

【摘要】：背景與目的:術(shù)后認(rèn)知功能障礙(postoperative cognitive dysfunction,POCD)是一種手術(shù)后發(fā)生在中樞神經(jīng)系統(tǒng)常見(jiàn)的并發(fā)癥,尤其在老年患者中發(fā)生率極高,其可導(dǎo)致患者出現(xiàn)長(zhǎng)期性或永久性的認(rèn)知功能損害,生活自理能力的下降,更嚴(yán)重時(shí)甚至喪失。值得重視的是:POCD的發(fā)生率還與患者術(shù)后遠(yuǎn)期死亡率成正相關(guān),給家庭及社會(huì)帶來(lái)較大的負(fù)擔(dān)。國(guó)內(nèi)外學(xué)者在POCD的發(fā)生機(jī)制及防治方面做了大量的工作,但其具體機(jī)制目前仍未完全闡明,也無(wú)理想的防治方法。研究認(rèn)為患者經(jīng)手術(shù)創(chuàng)傷后,可以誘發(fā)大腦出現(xiàn)局部自限性的炎癥或全身性炎癥(systemic inflammatory),后者是一種級(jí)聯(lián)式的瀑布樣炎癥反應(yīng),最終能導(dǎo)致POCD的發(fā)生及發(fā)展。小膠質(zhì)細(xì)胞是一種中樞神經(jīng)系統(tǒng)(Central Nervous System,CNS)固有的先天性免疫細(xì)胞,多年來(lái)被認(rèn)為參與了神經(jīng)退化疾病及神經(jīng)炎癥的病理過(guò)程。越來(lái)越多的證據(jù)表明創(chuàng)傷、外周炎癥等因素刺激小膠質(zhì)細(xì)胞,導(dǎo)致其激活后,其能釋放諸多神經(jīng)毒性物質(zhì),包括:腫瘤壞死因子(TNF)-α,白細(xì)胞介素(IL)-6,一氧化氮(NO)和活性氧(ROS)。這些毒性物質(zhì)相互促進(jìn)作用,導(dǎo)致了神經(jīng)細(xì)胞凋亡及損傷。小膠質(zhì)細(xì)胞涉及的細(xì)胞毒性因子也廣泛參與了多種組織器官缺血再灌注損傷、炎癥等多種病理生理過(guò)程,但其是否參與肝葉部分切除術(shù)所致的POCD的發(fā)生尚未見(jiàn)較多報(bào)道。針灸是我國(guó)傳統(tǒng)醫(yī)學(xué)的重要治療方法之一,具有操作簡(jiǎn)單,明確的功效,經(jīng)濟(jì)安全,無(wú)副作用等優(yōu)點(diǎn),已在國(guó)內(nèi)外醫(yī)療領(lǐng)域吸引了人們的廣泛關(guān)注。此外,根據(jù)病人的具體情況,可以通過(guò)選擇適當(dāng)?shù)难ㄎ贿M(jìn)行個(gè)性化治療以提高療效。電針(electroacupuncture,EA)刺激是在傳統(tǒng)針灸的基礎(chǔ)上、通過(guò)改變電刺激參數(shù)生效。事實(shí)證明,電針對(duì)心臟,腎臟和腦等器官損傷有預(yù)防和治療作用。它可以改善學(xué)習(xí)和記憶功能,調(diào)節(jié)免疫系統(tǒng)、抗炎、抗氧化、抗凋亡等。我們前期研究已證實(shí)EA能通過(guò)抑制小膠質(zhì)細(xì)胞激活,降低氧化損傷以及炎癥反應(yīng),防治肢體缺血再灌注后的腦損傷。電針參數(shù),通常包括脈沖輸出的波形、頻率和強(qiáng)度,是一個(gè)能明顯影響電針治療作用,并能改變其作用機(jī)制的重要因素。電針參數(shù)對(duì)治療效果有很大影響,能夠?qū)е聶C(jī)體出現(xiàn)的不同的治療反應(yīng)。因此,不同的疾病應(yīng)該選擇不同的參數(shù)以達(dá)到最好的療效。在先前的有關(guān)EA對(duì)中樞神經(jīng)系統(tǒng)影響的研究中,主要是使用的疏密波,少數(shù)研究則使用連續(xù)波或不連續(xù)波。然而,使用EA防治POCD的研究是有限的,不同波形電針對(duì)POCD的影響及其機(jī)制目前尚不清楚。因此,本實(shí)驗(yàn)擬采用老年大鼠行肝葉部分切除術(shù)所致的術(shù)后認(rèn)知功能障礙模型,探討小膠質(zhì)細(xì)胞在肝葉部分切除術(shù)所致POCD中的作用,同時(shí)研究不同波形EA防治老年大鼠肝葉部分切除術(shù)所致POCD的作用與小膠質(zhì)細(xì)胞的關(guān)系。本研究的完成有望為POCD發(fā)生及EA防治POCD機(jī)制注入新的內(nèi)容:一方面為防治POCD提供重要的可供干預(yù)的作用靶點(diǎn),有利于臨床針對(duì)小膠質(zhì)細(xì)胞開(kāi)發(fā)防治POCD的藥物;另一方面可為不同波形EA保護(hù)效應(yīng)提供理論基礎(chǔ)。方法:120只Wistar雄性老年大鼠,隨機(jī)分為5組(n=24):假手術(shù)組(S組)、手術(shù)組(O組)、電針連續(xù)波組(CW組)、電針疏密波組(DW組)、電針間斷波組(IW組)。建立肝葉部分切除模型,電針組于術(shù)前電針刺激“百會(huì)”穴和“大椎”穴,留針30 min,每日1次,連續(xù)治療3d。用Morris水迷宮評(píng)定大鼠術(shù)后1d、2d及5d認(rèn)知功能;于術(shù)后2d,取腦組織,用免疫組化法觀察海馬小膠質(zhì)細(xì)胞(MG)活化情況;采用Western blot法檢測(cè)MG標(biāo)志物Iba-1的表達(dá)水平;測(cè)定活性氧(ROS)、丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性、白細(xì)胞介素(IL)-1β、IL-6和腫瘤壞死因子(TNF)-α含量;通過(guò)原位末端標(biāo)記(TUNEL)法觀察腦細(xì)胞凋亡,計(jì)算凋亡指數(shù)。結(jié)果:(1)認(rèn)知功能:與S組比較,O組及電針各組大鼠術(shù)后1d、2d及5d的潛伏期和游泳距離顯著延長(zhǎng),穿越原平臺(tái)次數(shù)減少,差異有統(tǒng)計(jì)學(xué)意義(p0.05);與O組比較,CW、DW、IW三電針組潛伏期和游泳距離顯著縮短,穿越原平臺(tái)次數(shù)增加,差異有統(tǒng)計(jì)學(xué)意義(p0.05);CW、DW、IW組之間比較,潛伏期、游泳距離及穿越原平臺(tái)次數(shù)的差異均有統(tǒng)計(jì)學(xué)意義(p0.05),且DW組IW組CW組。(2)海馬組織中小膠質(zhì)細(xì)胞變化:與S組比較,O組及電針各組Iba-1陽(yáng)性細(xì)胞數(shù)、小膠質(zhì)細(xì)胞激活百分比及Iba-1蛋白表達(dá)增加,差異有統(tǒng)計(jì)學(xué)意義(p0.05);與O組比較,CW、DW、IW三組Iba-1陽(yáng)性細(xì)胞數(shù)、小膠質(zhì)細(xì)胞激活百分比及Iba-1蛋白表達(dá)量明顯降低,差異有統(tǒng)計(jì)學(xué)意義(p0.05);CW、DW、IW組之間比較,以上指標(biāo)差異均有統(tǒng)計(jì)學(xué)意義(p0.05)。DW最為顯著,IW次之,CW降幅較小。(3)海馬組織中IL-1β、IL-6及TNF-α濃度:與S組比較,O組及電針各組IL-1β、IL-6及TNF-α含量增加,有統(tǒng)計(jì)學(xué)差異(p0.05);與O組比較,CW、DW、IW三組IL-1β、IL-6及TNF-α含量降低,差異也有統(tǒng)計(jì)學(xué)意義(p0.05);CW、DW、IW組之間比較,以上指標(biāo)差異均有統(tǒng)計(jì)學(xué)意義(p0.05)。DW降低最明顯,IW次之,CW最小。(4)海馬組織中ROS、MDA含量和SOD活性:與S組比較,O組及電針各組ROS、MDA含量明顯增加、SOD活性明顯降低,差異有統(tǒng)計(jì)學(xué)意義(p0.05);與O組比較,CW、DW、IW三組ROS、MDA含量均降低、SOD活性均增強(qiáng)(p0.05);CW、DW、IW組之間比較,以上指標(biāo)差異均有統(tǒng)計(jì)學(xué)意義(p0.05)。DW降低最明顯,IW次之,CW最小。(5)海馬神經(jīng)細(xì)胞凋亡:S組可見(jiàn)極少量凋亡細(xì)胞;O組可見(jiàn)大量凋亡細(xì)胞。與S組比較,O組及電針各組凋亡指數(shù)顯著增加(p0.05);與O組比較,CW、DW、IW三組凋亡指數(shù)均降低,差異有統(tǒng)計(jì)學(xué)意義(p0.05);CW、DW、IW組之間比較,以上指標(biāo)差異均有統(tǒng)計(jì)學(xué)意義(p0.05)。DW降低最明顯,IW次之,CW最小。結(jié)論:1.肝葉部分切除術(shù)可以導(dǎo)致老年大鼠出現(xiàn)認(rèn)知功能障礙,誘發(fā)小膠質(zhì)細(xì)胞激活,促使海馬組織炎性因子、氧化應(yīng)激損傷及神經(jīng)細(xì)胞凋亡增加;2.不同波形電針刺激“百會(huì)”,“大椎”穴均可改善老年大鼠術(shù)后認(rèn)知功能障礙,以疏密波最佳,間斷波次之,連續(xù)波最差;3.電針預(yù)處理改善老年大鼠POCD的機(jī)制可能與抑制小膠質(zhì)細(xì)胞激活,減輕炎癥反應(yīng)、氧化應(yīng)激損傷及神經(jīng)細(xì)胞凋亡有關(guān)。
[Abstract]:Background and purpose: postoperative cognitive dysfunction (POCD) is a common complication occurring in the central nervous system after operation, especially in the elderly patients, which can lead to chronic or permanent cognitive impairment, the decline of self-care ability, and even more serious time. The loss. It is worth noting that the incidence of POCD is also positively related to the long-term mortality of the patients, bringing a greater burden to the family and society. Scholars at home and abroad have done a lot of work on the mechanism and prevention of POCD, but the specific mechanisms are still not fully elucidated and no ideal methods of prevention and control. After trauma, it can induce local self limiting inflammation or systemic inflammation (systemic inflammatory) in the brain, which is a cascade type of waterfall like inflammation that ultimately leads to the occurrence and development of POCD. Microglia is an inherent immune cell of the central nervous system (Central Nervous System, CNS) for many years. It is considered to be involved in the pathological process of neurodegenerative diseases and neuro inflammation. More and more evidence suggests that trauma, peripheral inflammation and other factors stimulate microglia, which can release many neurotoxic substances, including tumor necrosis factor (TNF) - alpha, IL -6, nitric oxide (NO) and reactive oxygen species (ROS). The mutual promotion of toxic substances leads to the apoptosis and damage of nerve cells. The cytotoxic factors involved in microglia are also widely involved in a variety of pathophysiological processes, such as ischemia-reperfusion injury and inflammation, but the involvement of POCD in partial hepatectomy has not yet been reported. One of the important treatment methods of traditional Chinese medicine has the advantages of simple operation, clear effect, economic safety and no side effect. It has attracted people's attention in the medical field at home and abroad. In addition, according to the specific situation of the patients, we can improve the curative effect by selecting appropriate acupoints for individualized treatment to improve the curative effect. (electroacupunctu Re, EA) stimulation is on the basis of traditional acupuncture and moxibustion by changing the parameters of electrical stimulation. In fact, it has been proved to have preventive and therapeutic effects on injury of heart, kidney and brain. It can improve learning and memory function, regulate immune system, anti-inflammatory, antioxidant, anti withering, and so on. Our previous study has confirmed that EA can inhibit microglia by inhibiting microglia. Cell activation, reducing oxidative damage and inflammatory reaction to prevent the brain damage after ischemia and reperfusion. Electroacupuncture Parameters, usually including pulse output waveform, frequency and intensity, are an important factor that can significantly affect the therapeutic effect of electroacupuncture and can change the mechanism of its action. The electroacupuncture parameters have a great influence on the therapeutic effect and can lead to the effect of the treatment. Different therapeutic responses to the body appear. Therefore, different diseases should choose different parameters to achieve the best effect. In previous studies on the effects of EA on the central nervous system, the main use of the dense wave, and the use of continuous or discontinuous waves in a few studies, but the use of EA to prevent and control POCD is limited. The effect of Electroacupuncture on POCD and its mechanism are still not clear. Therefore, this experiment is to use the model of postoperative cognitive dysfunction caused by partial hepatectomy in old rats, to explore the role of microglia in POCD caused by partial hepatectomy, and to study the prevention and treatment of partial hepatectomy by different wave forms of EA in old rats. The relationship between the role of POCD and microglia. The completion of this study is expected to infuse new contents for the occurrence of POCD and the mechanism of EA for the prevention and treatment of POCD. On the one hand, it provides an important target for intervention for the prevention and control of POCD, and is beneficial to the development of the drug for the development of the microglia for the prevention of POCD; on the other hand, it can provide the reason for the different waveform EA protection effects. Methods: 120 Wistar male aged rats were randomly divided into 5 groups (n=24): the sham operation group (group S), the operation group (group O), the electroacupuncture continuous wave group (group CW), the electroacupuncture group (group DW) and the intermittent wave group (group IW). The partial excision model of the hepatic lobe was established. The electroacupuncture group stimulated the "Baihui" point and the "Dazhui" point by Electroacupuncture before the operation, and the needle left 30 min, 1 daily, and daily 1. 3D. Morris water maze was used to evaluate the cognitive function of 1D, 2D and 5D in rats after operation. The activation of hippocampal microglia (MG) was observed by 2D and immunohistochemical method after operation, and the expression level of Iba-1 on MG marker was detected by Western blot method, and the activity of active oxygen (ROS), malondialdehyde and superoxide dismutase were measured by Western blot method. The content of interleukin (IL) -1 beta, IL-6 and tumor necrosis factor (TNF) - alpha, apoptosis and apoptosis index were observed by in situ terminal labeling (TUNEL) method. Results: (1) cognitive function: compared with the S group, the latency and swimming distance of 1D, 2D and 5D in the O group and the electroacupuncture group were significantly longer than those in the S group. Study significance (P0.05); compared with group O, the latency and swimming distance of CW, DW, IW three were significantly shortened, the number of crossing the original platform increased, the difference was statistically significant (P0.05); the difference between CW, DW, IW group, latency, swimming distance and the frequency of crossing the original platform were statistically significant (P0.05), and DW group IW group. (2) medium and small hippocampal tissue. Compared with the S group, the number of Iba-1 positive cells, the percentage of microglia activation and the expression of Iba-1 protein increased in group O and electroacupuncture, and the difference was statistically significant (P0.05). Compared with the O group, the number of Iba-1 positive cells in CW, DW, IW three groups, the percentage of activation of microglia and the expression of Iba-1 protein decreased significantly, and the difference was statistically significant. P0.05, CW, DW, and IW were statistically significant (P0.05).DW, IW time and CW decline. (3) the concentration of IL-1 beta, IL-6 and TNF- alpha in the hippocampus: compared with the S group, there was a statistical difference between the groups and the electroacupuncture groups. And TNF- alpha content decreased, the difference also had statistical significance (P0.05); CW, DW, IW group, the above index difference was statistically significant (P0.05).DW decrease most obvious, IW times, CW minimum. (4) ROS, MDA content and SOD activity in the hippocampus: compared with the group and Electroacupuncture groups Statistical significance (P0.05); compared with group O, CW, DW, IW three groups ROS, MDA content decreased, SOD activity increased (P0.05); CW, DW, there was a significant difference between the IW groups. (5) apoptosis of the hippocampal neurons: a large number of apoptotic cells in the group; and a large number of apoptotic cells. Compared with group S, apoptosis index of group O and electroacupuncture increased significantly (P0.05). Compared with group O, the apoptotic index in CW, DW, IW three groups decreased, the difference was statistically significant (P0.05); CW, DW, IW group had statistical significance (P0.05) was the most significant difference between the groups of CW, DW, IW. Conclusion: 1. partial hepatectomy can lead to old age. In rats, cognitive dysfunction, induced microglia activation, induced inflammatory factors in the hippocampus, oxidative stress injury and neuronal apoptosis increased; 2. different waveform electroacupuncture stimulation of "Baihui" and "Da Zhui" can improve the cognitive impairment of old rats after operation, with the best density wave, discontinuous wave, and the worst continuous wave; 3. electroacupuncture. The mechanism of pretreatment in improving POCD in aged rats may be related to inhibiting microglial activation, reducing inflammatory reaction, oxidative stress injury and neuronal apoptosis.
【學(xué)位授予單位】：西南醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R657.3

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