本文關(guān)鍵詞：大鼠下丘腦腹內(nèi)側(cè)核—伏隔核nesfatin-1通路構(gòu)成及胃功能調(diào)控研究　出處：《青島大學(xué)》2017年博士論文　論文類(lèi)型：學(xué)位論文

  更多相關(guān)文章： nesfatin-1 下丘腦腹內(nèi)側(cè)核 伏隔核 攝食 胃功能

【摘要】：目的:Nesfatin-1是新發(fā)現(xiàn)的一種能夠抑制攝食和胃運(yùn)動(dòng)的新型腦腸肽類(lèi)激素,廣泛分布于中樞神經(jīng)系統(tǒng)和胃腸道等外周器官�！帮柺持袠小毕虑鹉X腹內(nèi)側(cè)核是調(diào)控?cái)z食的重要核團(tuán);伏隔核參與獲取食物和進(jìn)食沖動(dòng)的調(diào)控,兩個(gè)核團(tuán)中均有nesfatin-1的表達(dá)。目前下丘腦腹內(nèi)側(cè)核和伏隔核中nesfatin-1對(duì)攝食和胃酸分泌、胃運(yùn)動(dòng)、胃排空等胃功能的調(diào)控作用仍不清楚。本實(shí)驗(yàn)將研究集中于下丘腦腹內(nèi)側(cè)核和伏隔核:①觀察胃擴(kuò)張對(duì)下丘腦腹內(nèi)側(cè)核內(nèi)nesfatin-1免疫陽(yáng)性神經(jīng)元活性的影響;研究伏隔核→下丘腦腹內(nèi)側(cè)核nesfatin-1神經(jīng)通路的構(gòu)成;②探討nesfatin-1對(duì)下丘腦腹內(nèi)側(cè)核內(nèi)胃擴(kuò)張敏感神經(jīng)元電生理活性的影響,進(jìn)一步觀察伏隔核對(duì)下丘腦腹內(nèi)側(cè)核內(nèi)胃擴(kuò)張敏感神經(jīng)元的調(diào)控作用,闡明伏隔核→下丘腦腹內(nèi)側(cè)核nesfatin-1功能通路的構(gòu)成;③探討下丘腦腹內(nèi)側(cè)核nesfatin-1對(duì)攝食、胃酸分泌、胃運(yùn)動(dòng)和胃排空的調(diào)控作用,以及伏隔核→下丘腦腹內(nèi)側(cè)核nesfatin-1通路對(duì)腹內(nèi)側(cè)核功能的影響,補(bǔ)充和完善攝食和胃功能調(diào)控的中樞機(jī)制。方法:1.采用熒光免疫組織化學(xué)方法,觀察nesfatin-1在下丘腦腹內(nèi)側(cè)核表達(dá)及胃擴(kuò)張對(duì)nesfatin-1神經(jīng)元的激活作用;采用熒光金逆行追蹤結(jié)合熒光免疫組化技術(shù),觀察伏隔核→下丘腦腹內(nèi)側(cè)核nesfatin-1神經(jīng)通路的構(gòu)成。2.采用細(xì)胞表面微量注射藥物、腦核團(tuán)電刺激、神經(jīng)元胞外記錄等方法,觀察nesfatin-1、黑皮質(zhì)素3/4受體拮抗劑SHU9119以及電刺激伏隔核對(duì)下丘腦腹內(nèi)側(cè)核胃擴(kuò)張敏感神經(jīng)元電生理活動(dòng)的影響。3.采用核團(tuán)微量注射藥物、腦核團(tuán)電刺激、攝食量記錄、胃酸滴定測(cè)量、在體胃運(yùn)動(dòng)和胃排空酚紅定量測(cè)定等方法,觀察下丘腦腹內(nèi)側(cè)核微量注射nesfatin-1以及電刺激伏隔核對(duì)清醒大鼠攝食量、胃酸分泌、胃運(yùn)動(dòng)和胃排空的影響。結(jié)果:1.大鼠下丘腦腹內(nèi)側(cè)核內(nèi)存在nesfatin-1免疫陽(yáng)性神經(jīng)元;胃擴(kuò)張刺激腹內(nèi)側(cè)核nesfatin-1免疫陽(yáng)性神經(jīng)元中c-Fos表達(dá)增多,細(xì)胞活性增強(qiáng)。2.下丘腦腹內(nèi)側(cè)核中注射熒光金可逆行至伏隔核,且存在熒光金與nesfatin-1免疫陽(yáng)性神經(jīng)元共染,提示伏隔核與下丘腦腹內(nèi)側(cè)核間存在向下丘腦腹內(nèi)側(cè)核投射的神經(jīng)纖維,且部分投射纖維由nesfatin-1免疫陽(yáng)性神經(jīng)元發(fā)出延伸至下丘腦腹內(nèi)側(cè)核。3.腹內(nèi)側(cè)核共記錄到64個(gè)胃擴(kuò)張敏感神經(jīng)元,其中35個(gè)神經(jīng)元(54.70%)為胃擴(kuò)張興奮神經(jīng)元(GD-E),29個(gè)神經(jīng)元(45.3%)為胃擴(kuò)張抑制神經(jīng)元(GD-I),提示下丘腦腹內(nèi)側(cè)核可接受來(lái)自胃部的傳入信息。4.腹內(nèi)側(cè)核微量注射nesfatin-1,24.14%的GD-I神經(jīng)元興奮,放電頻率從2.45 ± 0.37 Hz升高到3.82 ±0.56 Hz(p0.05);22.86%的GD-E神經(jīng)元被抑制,放電頻率從 2.77 ±0.39 降低到 1.67± 0.37 Hz(p0.05)。Nesfatin-1 對(duì)胃擴(kuò)張敏感神經(jīng)元的影響可被腹內(nèi)側(cè)核預(yù)先注射黑皮質(zhì)素3/4受體拮抗劑SHU9119部分阻斷(p0.05)。5.電刺激伏隔核,腹內(nèi)側(cè)核胃擴(kuò)張敏感神經(jīng)元中的59.26%GD-I神經(jīng)元興奮,放電頻率從2.33 ± 0.57 Hz升高到3.45 ± 0.34 Hz(p0.05);此作用可被腹內(nèi)側(cè)核預(yù)先注射nesfatin-1抗體部分阻斷(p0.05);電刺激伏隔核,53.06%的GD-E神經(jīng)元興奮,放電頻率從2.74 ±0.71 Hz增加到5.08 ±1.15 Hz(p0.05);腹內(nèi)側(cè)核中預(yù)先注射nesfatin-1抗體可進(jìn)一步增強(qiáng)GD-E神經(jīng)元興奮性,放電頻率升至6.81 ± 1.13 Hz(p0.05)。腹內(nèi)側(cè)核單獨(dú)注射nesfatin-1抗體或生理鹽水GD神經(jīng)元放電活動(dòng)無(wú)顯著改變(p0.05)。6.腹內(nèi)側(cè)核注射低劑量nesfatin-1,大鼠2h內(nèi)攝食量顯著減少,注射高劑量的nesfatin-1,攝食量的減少可持續(xù)約4-6h;腹內(nèi)側(cè)核注射nesfatin-1,由皮下注射2-脫氧-D-葡萄糖引起的胃酸分泌也受到顯著抑制(48.63 ± 10.21%);注射nesfatin-1后約4 min,大鼠胃運(yùn)動(dòng)開(kāi)始下降,15 min達(dá)最低點(diǎn),下降(35.2 ± 8.9%,p0.05);腹內(nèi)側(cè)核注射nesfatin-1,大鼠胃排空顯著減弱,排空率降至50.15 ±15.6%(p0.05);腹內(nèi)側(cè)核預(yù)先給予黑皮質(zhì)素3/4受體拮抗劑SHU9119,可部分阻斷腹內(nèi)側(cè)核注射nesfatin-1對(duì)攝食和胃功能的抑制效應(yīng)(p0.05)。7.20μA低電流刺激大鼠伏隔核,大鼠攝食無(wú)顯著改變(P0.05),但采用50μA高電流刺激伏隔核,2-6h間大鼠的累積攝食量均低于假電刺激組(p0.05),且2-脫氧-D-葡萄糖誘導(dǎo)的胃酸分泌增多也受到顯著抑制(9.16 ±1.53降至5.52± 0.88 μEq/15min,p0.05);50 μA高電流刺激伏隔核,大鼠胃運(yùn)動(dòng)MI%值降至假電刺激對(duì)照組的72.25 ±9.82%(p0.05);胃排空率也減少為假電刺激對(duì)照組的68.36 ±8.79%(0.05)。下丘腦腹內(nèi)側(cè)核預(yù)先注射nesfatin-1抗體,可消弱電刺激伏隔核抑制大鼠攝食、胃酸分泌和胃動(dòng)力效應(yīng)(P0.05)。下丘腦腹內(nèi)側(cè)核單獨(dú)注射nesfatin-1抗體或NS對(duì)大鼠攝食量、胃酸分泌量和胃動(dòng)力無(wú)顯著影響(0.05)。結(jié)論:1.下丘腦腹內(nèi)側(cè)核有nesfatin-1免疫陽(yáng)性神經(jīng)元表達(dá),且胃擴(kuò)張可改變部分nesfatin-1神經(jīng)元活性;2.伏隔核內(nèi)nesfatin-1免疫陽(yáng)性神經(jīng)元可發(fā)出神經(jīng)纖維投射至下丘腦腹內(nèi)側(cè)核,形成伏隔核-下丘腦腹內(nèi)側(cè)核nesfatin-1神經(jīng)通路;3.下丘腦腹內(nèi)側(cè)核可接受胃來(lái)源的信號(hào),nesfatin-1可影響這些胃來(lái)源信號(hào)的傳入,并可通過(guò)改變傳出沖動(dòng)參與食物攝取、胃酸分泌、胃運(yùn)動(dòng)以及冒排空等功能的調(diào)控;4.Nesfatin-1在伏隔核-下丘腦腹內(nèi)側(cè)核通路可調(diào)控大鼠攝食、胃酸分泌、胃運(yùn)動(dòng)以及胃排空,這提示,伏隔核和下丘腦腹內(nèi)側(cè)核間有nesfatin-1功能通路存在。
[Abstract]:Objective: Nesfatin-1 is capable of inhibiting food intake and gastric motility model of brain gut peptide hormone newly discovered, widely distributed in the central nervous system and peripheral organs such as gastrointestinal tract. "Satiety center" in the ventromedial hypothalamic nucleus is an important nucleus in the regulation of food intake; the nucleus accumbens in obtaining food and eating impulse control, expression nesfatin-1 has two nuclei. The ventromedial hypothalamic nucleus and nucleus accumbens nesfatin-1 on food intake and gastric acid secretion, gastric motility, gastric emptying and gastric function regulation remains unclear. This study will focus on the ventromedial hypothalamic nucleus and nucleus accumbens: To observe gastric dilatation effect on the ventral hypothalamus the medial nucleus of nesfatin-1 immunoreactive neuronal activity; V septum, a study of the ventromedial hypothalamic nucleus nesfatin-1 neural pathway; the effects of nesfatin-1 on hypothalamic ventromedial nucleus in the stomach by the expansion of Aman Chang's sense of God Effect of electrophysiological activity, further observe the regulation of nucleus accumbens ventromedial hypothalamic nucleus on gastric distension sensitive neurons, which clarify the nucleus accumbens, ventromedial hypothalamus nesfatin-1 pathway; to explore the ventromedial hypothalamic nucleus nesfatin-1 on gastric acid secretion, feeding, regulation of gastric motility and gastric emptying, and V septal nucleus, ventromedial hypothalamic nucleus nesfatin-1 pathway influence on the function of the ventromedial nucleus, supplement and perfect the central mechanism of feeding and regulation of gastric function. Methods: 1. using immunohistochemistry method to observe the effect of nesfatin-1 on activation of nesfatin-1 neurons in the ventromedial hypothalamic nucleus expression and gastric dilatation; using Fluorogold retrograde tracing combined with fluorescence immunohistochemistry observation of nucleus accumbens, ventromedial hypothalamic nucleus nesfatin-1 neural pathway composed of.2. cell surface by microinjection of drugs, brain nuclei Group of electrical stimulation, extracellular neural recording method, observation of nesfatin-1,.3. of melanocortin 3/4 receptor antagonist SHU9119 and stimulation of nucleus accumbens ventromedial hypothalamic nucleus on gastric distension sensitive neurons electrophysiological activity by nucleus microinjection of drugs, brain stimulation, food intake records, acid titration measurements in vivo gastric motility and gastric emptying by quantitative analysis, observation of the ventromedial hypothalamic nucleus microinjection of nesfatin-1 and stimulation of nucleus accumbens in conscious rats food intake, gastric acid secretion, affect gastric motility and gastric emptying. Results: 1. rat ventromedial hypothalamic nucleus nesfatin-1 immunoreactive neurons; gastric distension stimulation increased the expression of c-Fos the ventromedial nucleus of nesfatin-1 immunoreactive neurons, enhance.2. cell activity in the ventromedial hypothalamic nucleus injection of fluorogold reversible to the nucleus accumbens, and the presence of fluorescent gold and nesfatin-1 Immunoreactive neurons were stained, suggesting that the nucleus accumbens and the ventromedial hypothalamic nucleus between the hypothalamic ventromedial nucleus projecting to the nerve fibers, and the portion of the projection fibers by nesfatin-1 immunoreactive neurons by extending to the ventromedial hypothalamic ventromedial nucleus of 64.3. neurons were recorded in the expansion of Zhang Mingan's stomach, of which 35 neurons (54.70%) for gastric dilatation (GD-E) neurons, 29 neurons (45.3%) neurons for dilatation of the stomach (GD-I), suggesting that the ventromedial hypothalamic nucleus can receive afferent signals from the ventromedial nucleus of.4. microinjection of nesfatin-1,24.14% from stomach GD-I neurons, discharge frequency from 2.45 + 0.37 Hz + 0.56 Hz (up to 3.82 P0.05 22.86%); the GD-E neurons were inhibited, the discharge frequency is reduced to 1.67 from 2.77 + 0.39 + 0.37 Hz (P0.05) effect of.Nesfatin-1 on gastric distension sensitive neurons in the ventromedial nucleus can be pre injection Melanocortin 3/4 receptor antagonist SHU9119 partially blocked (P0.05).5. electrical stimulation of nucleus accumbens, ventral medial nucleus of gastric distension sensitive neurons in 59.26%GD-I neurons, discharge frequency from 2.33 + 0.57 to 3.45 + 0.34 Hz Hz increased (P0.05); this effect could be the ventromedial nucleus of pre injection of nesfatin-1 antibody partially blocked (P0.05); electrical stimulation of nucleus accumbens neurons, 53.06% GD-E, discharge frequency from 2.74 + 0.71 to 5.08 + 1.15 Hz Hz (P0.05); ventromedial nucleus in the pre injection of nesfatin-1 antibody can further enhance the excitability of GD-E neurons, discharge frequency to 6.81 + 1.13 Hz (P0.05). No significant change in ventromedialis nuclear single injection of nesfatin-1 antibody or normal saline GD neurons (P0.05) low dose nesfatin-1.6. nucleus ventromedialis injection in 2h of rats significantly reduced food intake, high dose of nesfatin-1 injection, the reduction of food intake to renew 4-6h; ventromedial nucleus nesfatin-1 injection induced by subcutaneous injection of 2- deoxy -D- glucose acid secretion was also significantly inhibited (48.63 + 10.21%); nesfatin-1 after injection of about 4 min, gastric motility of rats began to decline 15, the lowest level at Min, decreased (35.2 + 8.9%, P0.05); ventromedial nucleus injection of nesfatin-1. Gastric emptying in rats decreased and the emptying rate dropped to 50.15 + 15.6% (P0.05); ventromedial pre administration of melanocortin 3/4 receptor antagonist SHU9119 partially blocked the inhibitory effect of nucleus ventromedialis injection of nesfatin-1 on food intake and gastric function (P0.05).7.20 A low current stimulation of rat nucleus accumbens, feeding rats no significant change (P0.05), but by 50 A high current stimulation of the nucleus accumbens, 2-6h rats cumulative food intake were lower than the sham stimulation group (P0.05), and 2- deoxy -D- glucose induced increase in gastric acid secretion was significantly inhibited (9.16 + 1.53 to 5.52 + 0.88 Eq/15min, P0.05); 50 A high current stimulation of nucleus accumbens, gastric motility in rats MI% decreased to sham stimulation control group 72.25 + 9.82% (P0.05); gastric emptying rate also reduces the false stimulation control group 68.36 + 8.79% (0.05). The ventromedial hypothalamic nucleus pre injection of nesfatin-1 antibody. Electrical stimulation of nucleus accumbens can weaken the inhibition of feeding rats, gastric acid secretion and gastric motility effect (P0.05). The ventromedial hypothalamic nucleus in single injection of nesfatin-1 antibody or NS on food intake of rats, gastric acid secretion and gastric motility had no significant effect (0.05). Conclusion: 1. the ventromedial hypothalamic nucleus expression of nesfatin-1 immunoreactive neurons and, the stomach expansion can change part of the activity of nesfatin-1 neurons; 2. immunoreactive neurons in the nucleus accumbens nesfatin-1 can send nerve fibers to the ventromedial hypothalamic nucleus, forming the nucleus accumbens - ventromedial hypothalamus nesfatin-1 neural pathway; 3. ventromedial hypothalamic nucleus Acceptable signal gastric sources, nesfatin-1 can influence the introduction of the source of gastric signal, and by changing the efferent impulses in food intake, gastric acid secretion, gastric motility and emptying function of risk control; 4.Nesfatin-1 in the nucleus accumbens - ventromedial hypothalamic pathway regulation of rat feeding, gastric motility and gastric acid secretion. Emptying, which suggests that the nucleus accumbens and the ventromedial hypothalamic nucleus there exist the nesfatin-1 pathway.

【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R33

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