發(fā)布時(shí)間：2018-09-01 09:23

【摘要】：研究背景 急性胃粘膜損傷(Acute Gastric Mucosal Lesion, AGML)是臨床上重大手術(shù)應(yīng)激、嚴(yán)重?zé)齽?chuàng)傷或者危重癥患者的常見并發(fā)癥,AGML的發(fā)病機(jī)制與機(jī)體神經(jīng)體液失調(diào)、胃粘膜的防御功能減弱以及損傷因素增強(qiáng)等因素密切相關(guān)。雖然影響AGML的發(fā)生、發(fā)展因素非常復(fù)雜,但持續(xù)性、過度傷害應(yīng)激是誘發(fā)急性胃粘膜損傷發(fā)生、發(fā)展的最直接、最重要的因素。在嚴(yán)重創(chuàng)傷條件下,各種應(yīng)激因素作用于胃腸道和中樞神經(jīng)系統(tǒng),通過內(nèi)分泌、神經(jīng)、免疫等系統(tǒng)與消化道(消化道神經(jīng)、內(nèi)分泌網(wǎng)絡(luò)調(diào)控)相互作用而產(chǎn)生胃粘膜病變。大量的文獻(xiàn)已證實(shí),在嚴(yán)重的應(yīng)激狀態(tài)下,由于胃粘膜能量代謝障礙、酸堿平衡紊亂、胃粘膜屏障功能破壞以及自由基產(chǎn)生增多,最終導(dǎo)致胃粘膜局部出現(xiàn)嚴(yán)重的血液循環(huán)障礙,主要表現(xiàn)為胃粘膜的微循環(huán)障礙以及胃血流量減少。已有研究表明,胃的脊髓傳入神經(jīng)通路內(nèi)以及胃腸道分布有豐富的TRPV1受體及辣椒素敏感傳入神經(jīng)元,它們?cè)诰S持胃腸黏膜的正常功能、對(duì)抗多種傷害性侵襲因素中發(fā)揮重要的作用。我們前期研究結(jié)果表明,TRPV1在應(yīng)激性急性胃粘膜損傷的發(fā)生中起重要作用,本研究旨在從舒芬太尼預(yù)先給藥以及浸水束縛應(yīng)激不同時(shí)間的角度探討TRPV1在應(yīng)激性AGML中的作用及機(jī)制。 舒芬太尼(Sufentail)是一種以激活μ受體為主的阿片類麻醉鎮(zhèn)痛藥,其脂溶性高,能夠迅速通過血-腦屏障進(jìn)入腦內(nèi)與阿片類受體結(jié)合發(fā)揮作用。我們前期動(dòng)物實(shí)驗(yàn)證實(shí),TRPV1和μ-阿片受體在胃的脊髓控制區(qū)的脊髓背根神經(jīng)節(jié)(DRG)上共存表達(dá),且二者功能上具有相關(guān)性；另有文獻(xiàn)指出,向腦室內(nèi)注射選擇性μ-阿片受體激動(dòng)劑可以減少酒精或吲哚美辛等誘導(dǎo)的急性胃粘膜損傷。因此本實(shí)驗(yàn)第一部分?jǐn)M探索舒芬太尼預(yù)處理在WIRS誘導(dǎo)的AGML中的作用機(jī)制及其與TRPV1的關(guān)系。 由于急性胃粘膜損傷是臨床上急危重患者的常見并發(fā)癥,且已有文獻(xiàn)證實(shí)TRPV1在胃脊髓傳入神經(jīng)通路以及胃粘膜都高表達(dá),且我們前期研究表明TRPV1、ASIC3在胃脊髓控制區(qū)DRG神經(jīng)元上共存表達(dá),它們?cè)趹?yīng)激性急性AGML的發(fā)生中起重要作用。本課題采用實(shí)時(shí)熒光定量PCR、免疫組化等方法,分別從下丘腦和胃粘膜二個(gè)層面探討TRPV1在AGML發(fā)生中的作用及可能機(jī)制,并從應(yīng)激控制的角度采用舒芬太尼預(yù)先給藥進(jìn)行反證,旨在獲得TRPV1參與和調(diào)控應(yīng)激性AGML形成的可靠證據(jù)。本實(shí)驗(yàn)亦從WIRS不同時(shí)間的角度探索胃粘膜TRPV1、ASIC3mRNA的動(dòng)態(tài)變化過程,并計(jì)數(shù)胃粘膜損傷潰瘍指數(shù)(UI),同時(shí)檢測(cè)應(yīng)激不同時(shí)間時(shí)血清SOD、MDA的活力水平,觀察大鼠應(yīng)激狀態(tài)下機(jī)體氧化和抗氧化能力。結(jié)果表明應(yīng)激性潰瘍發(fā)生過程中SOD、MDA可作為一個(gè)早期敏感指標(biāo)進(jìn)行檢測(cè),能夠?yàn)榕R床上選擇合適的時(shí)間對(duì)應(yīng)激性潰瘍進(jìn)行干預(yù)提供依據(jù)。通過初步探索TRPV1、ASIC3在AGML發(fā)生中的調(diào)控作用及其機(jī)制,為確立TRPV1作為防治應(yīng)激性AGML的新靶點(diǎn)提供更充分的科學(xué)依據(jù),也為圍術(shù)期應(yīng)激控制防治AGML的發(fā)生奠定堅(jiān)實(shí)的基礎(chǔ)。通過WIRS潰瘍模型的復(fù)制,我們更好地了解AGML的發(fā)病機(jī)理,為臨床上更好防治嚴(yán)重?zé)齽?chuàng)傷、手術(shù)和急危重患者高AGML提供新思路。 研究目的 通過復(fù)制經(jīng)典浸水束縛應(yīng)激模型,初步探索：1.TRPV1在應(yīng)激性急性胃粘膜損傷中的作用,并以舒芬太尼從中樞和外周兩個(gè)層面進(jìn)行驗(yàn)證,明確TRPV1mRNA與μ-阿片受體激動(dòng)劑之間的關(guān)系,同時(shí)檢測(cè)大鼠應(yīng)激性AGML過程中胃粘膜及血清中SOD和MDA的水平,觀察機(jī)體在應(yīng)激過程中的抗氧化能力；2.從浸水束縛應(yīng)激不同時(shí)間的角度探討胃粘膜層面TRPV1mRNA和ASIC3mRNA之間的關(guān)系以及機(jī)體的氧化和抗氧化能力變化。 實(shí)驗(yàn)方法 (1)成年雄性SPF級(jí)Wistar大鼠30只,隨機(jī)分為3組,分別為：正常組(NC組)、浸水束縛應(yīng)激組(WIRS組)和舒芬太尼預(yù)先給藥組(SF組)。舒芬太尼預(yù)先給藥組在大鼠束縛浸水5min前腹腔注射25μg/kg舒芬太尼,WIRS組以等容積生理鹽水進(jìn)行腹腔注射；浸水束縛應(yīng)激(WIRS)模型制作參照以往研究方法。實(shí)驗(yàn)內(nèi)容包括：1各組大鼠麻醉后刮取胃粘膜、取下丘腦液氮凍存,提取組織總RNA,采用實(shí)時(shí)熒光定量PCR的方法檢測(cè)胃粘膜、下丘腦TRPV1mRNA的表達(dá)變化；2留取胃液后沖洗凈胃內(nèi)容物,顯微鏡下觀察胃粘膜損傷情況,計(jì)數(shù)潰瘍指數(shù)(UI),檢測(cè)胃液pH,觀察舒芬太尼對(duì)大鼠應(yīng)激性急性胃粘膜病變的作用；3各組胃組織損傷明顯處用組織剪剪取0.2×0.1cm大小組織塊,中性福爾馬林溶液固定,采用HE染色方法觀察舒芬太尼預(yù)先給藥對(duì)WIRS大鼠胃粘膜組織形態(tài)的影響；4各組大鼠麻醉后取其腹主動(dòng)脈血,離心并留取血清；測(cè)定胃粘膜MDA蛋白濃度,以檢測(cè)各組大鼠組織和血清中SOD、MDA含量； (2)成年雄性SPF級(jí)Wistar大鼠12只,隨機(jī)分為3組,分別為：正常組(NC組)、浸水束縛應(yīng)激組(WIRS組)和舒芬太尼預(yù)先給藥組(SF組),采用免疫組化技術(shù)觀察TRPV1在胃組織的定位及表達(dá)變化。 (3)成年雄性SPF級(jí)Wistar大鼠40只,隨機(jī)分為4組,分別為：正常組(NC組)、浸水束縛應(yīng)激2h組(WIRS2h組)、浸水束縛應(yīng)激4h組(WIRS4h組)和浸水束縛應(yīng)激6h組(WIRS6h組),內(nèi)容包括：1各組大鼠麻醉后刮取胃粘膜液氮凍存,提取組織總RNA,采用實(shí)時(shí)熒光定量PCR的方法檢測(cè)浸水束縛應(yīng)激不同時(shí)間胃粘膜TRPV1mRNA和ASIC3mRNA的表達(dá)變化；2沖洗凈胃內(nèi)容物,顯微鏡下觀察胃粘膜損傷情況,計(jì)數(shù)潰瘍指數(shù)(UI)；3各組胃組織損傷明顯處用組織剪剪取0.2×0.1cm大小組織塊,中性福爾馬林溶液固定,采用HE染色方法觀察浸水束縛應(yīng)激不同時(shí)間大鼠胃組織形態(tài)的變化；4各組大鼠麻醉后取其腹主動(dòng)脈血,離心并留取血清,以檢測(cè)不同時(shí)間點(diǎn)大鼠血清SOD、MDA含量。 實(shí)驗(yàn)結(jié)果 (1)NC組大鼠胃腔內(nèi)見少量棕灰色食物殘?jiān)?胃液呈透明淡黃色,沖洗后見胃粘膜光滑完整,呈淡紅色,未見水腫及出血。WIRS組大鼠胃腔內(nèi)見大量紅褐色內(nèi)容物及血性積液,沖洗后見胃粘膜明顯水腫,伴隨點(diǎn)狀、條索狀出血、糜爛甚至潰瘍。SF預(yù)處理組大鼠胃腔內(nèi)容物呈棕色,胃粘膜粘液增厚,偶見點(diǎn)狀及線狀出血點(diǎn),損傷較WIRS組明顯減輕。光鏡下觀察NC組大鼠腺體排列整齊,結(jié)構(gòu)完整,未見細(xì)胞結(jié)構(gòu)改變；WIRS組大鼠胃粘膜細(xì)胞排列紊亂,黏膜上皮黏膜脫落、壞死,細(xì)胞間隙增寬,無法辨認(rèn)腺體及具體結(jié)構(gòu)；舒芬太尼預(yù)先給藥組則明顯減輕胃粘膜層損傷程度,但仍有腺體結(jié)構(gòu)排列紊亂。浸水束縛應(yīng)激6h可引起大鼠胃粘膜損傷的潰瘍指數(shù)顯著升高(P0.05),舒芬太尼預(yù)先給藥可顯著降低UI(P0.05),但仍高于正常組。WIRS組胃液pH值顯著低于正常組(P0.05),舒芬太尼預(yù)先給藥組與正常組相比大鼠胃液pH值變化不明顯,顯著高于WIRS組。舒芬太尼預(yù)先給藥可明顯減少浸水束縛應(yīng)激引起的脂質(zhì)過氧化產(chǎn)物含量和胃粘膜組織局部SOD活力(P0.05),但血清SOD活力水平在各組間變化不明顯。熒光定量PCR結(jié)果顯示,應(yīng)激組胃粘膜TRPV1mRNA的相對(duì)表達(dá)量是正常組的(0.2±0.3)倍,而舒芬太尼預(yù)先給藥組TRPV1mRNA的表達(dá)則是正常組的(4.2+0.5)倍,兩組差異均有顯著性(P0.05)；下丘腦內(nèi),舒芬太尼預(yù)先給藥組TRPV1mRNA的相對(duì)表達(dá)量是正常組的(3.2±0.8)倍,差異亦具有統(tǒng)計(jì)學(xué)意義(P0.05),正常組與應(yīng)激組相比TRPV1mRNA則變化不明顯。 (2)免疫組化檢測(cè)結(jié)果顯示棕色顆粒為TRPV1受體的陽性表達(dá),結(jié)構(gòu)顯示,浸水束縛應(yīng)激模型組大鼠胃組織TRPV1受體的表達(dá)量略高于正常組大鼠,而舒芬太尼預(yù)先給藥組大鼠TRPV1受體的表達(dá)量顯著高于應(yīng)激組和正常組(P0.05)。 (3)熒光定量PCR結(jié)果顯示,胃粘膜TRPV1mRNA在WIRS2h和WIRS4h時(shí)變化不明顯,但在WIRS6h時(shí)顯著減低(P0.05)；與NC組相比,ASIC3mRNA相對(duì)表達(dá)量在應(yīng)激初期即出現(xiàn)明顯升高(P0.05)；與NC組、WIRS2h、 WIRS4h和WIRS6h相比,ASIC3mRNA在WIRS6h時(shí)明顯降低(P0.05)。各組大鼠胃沿大彎剪開沖洗后,見正常組大鼠胃粘膜光滑完整,呈淡紅色,無充血及水腫。WIRS2h及WIRS4h組大鼠胃內(nèi)容物呈褐色,沖洗時(shí)偶見出血點(diǎn)及糜爛,且WIRS2h組程度不及WIRS4h組,偶見出血點(diǎn)及條索狀潰瘍；WIRS6h組大鼠胃腔內(nèi)見大量紅褐色內(nèi)容物,沖洗時(shí)見紅色血痂,胃粘膜充血水腫,呈點(diǎn)狀、片狀糜爛壞死,多與胃縱軸平行。WIRS2h、4h、6h引起潰瘍指數(shù)升高(13.00±2.24vs0.00±0.00、16.40±3.05vs0.00±0.00、30.40±2.41vs0.00±0.00,P0.05),明顯高于NC組。胃粘膜損傷指數(shù)傾向于隨著WIRS時(shí)間的延長(zhǎng)而逐漸增加。血清SOD活力在應(yīng)激過程中先增高后降低,WIRS4h時(shí)最高,同時(shí)檢測(cè)到的MDA水平在WIRS4h時(shí)最低。WIRS2h、 WIRS4h、WIRS6h組胃粘膜內(nèi)TRPV1mRNA的相對(duì)表達(dá)量分別是正常組胃粘膜TRPV1mRNA的(1.43±0.19)、(1.20±0.13)和(0.19±0.03)倍。與NC組比較,胃粘膜WIRS6h組的TRPV1mRNA表達(dá)減少,其差別具有顯著統(tǒng)計(jì)學(xué)意義(P0.05)。 實(shí)驗(yàn)結(jié)論 (1)舒芬太尼預(yù)先給藥可有效減輕WIRS誘導(dǎo)的急性胃粘膜損傷,其機(jī)制可能與控制機(jī)體氧化應(yīng)激反應(yīng)、減少胃酸分泌以及調(diào)控中樞和外周TRPV1mRNA的表達(dá)有關(guān)。 (2)應(yīng)激性潰瘍發(fā)生過程中,機(jī)體存在一個(gè)代償過程,血清SOD、MDA水平可作為一個(gè)早期指標(biāo)進(jìn)行檢測(cè),為選擇合適的時(shí)間對(duì)應(yīng)激性潰瘍進(jìn)行干預(yù)提供依據(jù)。 (3)TRPV1和ASIC3在應(yīng)激性急性胃粘膜病變的過程中發(fā)揮一定的作用,二者的變化趨勢(shì)具有一致性。對(duì)于WIRS誘導(dǎo)的急性胃粘膜損傷,ASIC3比TRPV1更為敏感。
[Abstract]:Research background
Acute Gastric Mucosal Lesion (AGML) is a common complication of severe surgical stress, severe burns or critical illnesses. The pathogenesis of AGML is closely related to neurohumoral disorders, impaired gastric mucosal defense and increased injury factors. The factors are very complicated, but persistent, and excessive injury stress is the most direct and important factor that induces the occurrence and development of acute gastric mucosal injury. A large number of literatures have confirmed that under severe stress, gastric mucosal microcirculation disorder is the main manifestation of gastric mucosal hemodynamic disturbance due to disturbance of energy metabolism, disorder of acid-base balance, destruction of gastric mucosal barrier function and increase of free radicals. Previous studies have shown that there are abundant TRPV1 receptors and capsaicin-sensitive afferent neurons in the spinal afferent pathway and gastrointestinal tract of the stomach, which play an important role in maintaining the normal function of gastrointestinal mucosa and resisting multiple noxious invasion factors. The purpose of this study was to investigate the role and mechanism of TRPV1 in stress-induced acute gastric mucosal injury (SAGML) from the perspective of sufentanil pretreatment and immersion restraint stress at different times.
Sufentail is an opioid anesthetic analgesic drug that activates mu receptors. It is highly liposoluble and can quickly enter the brain through the blood-brain barrier to bind to opioid receptors. Our previous animal experiments confirmed that TRPV1 and mu-opioid receptors coexist in the dorsal root ganglion (DRG) of the spinal cord in the spinal cord control region of the stomach. The first part of this study is to explore the mechanism of sufentanil preconditioning in WIRS-induced AGML and its relationship with TRPV1.
Acute gastric mucosal injury is a common complication in critically ill patients, and the expression of TRPV1 in gastro-spinal afferent pathway and gastric mucosa has been proved to be high. Our previous studies showed that TRPV1 and ASIC3 coexist in DRG neurons in the gastro-spinal control region, and they play an important role in the pathogenesis of stress-induced acute AGML. In this study, real-time fluorescence quantitative PCR and immunohistochemistry were used to investigate the role and possible mechanism of TRPV1 in the development of AGML from hypothalamus and gastric mucosa, and sufentanil was used to pre-administer sufentanil in order to obtain reliable evidence that TRPV1 participated in and regulated the formation of stress-induced AGML. The dynamic changes of TRPV1 and ASIC3 mRNA in gastric mucosa were investigated by WIRS at different time points. The ulcer index (UI) of gastric mucosa injury was counted. The activities of SOD and MDA in serum were measured at different time points of stress. The oxidative and antioxidative abilities of rats were observed under stress conditions. As an early sensitive index, it can provide basis for choosing appropriate time to intervene stress ulcer in clinic. Through preliminary exploration of the regulatory role and mechanism of TRPV1 and ASIC3 in the occurrence of AGML, it can provide sufficient scientific basis for establishing TRPV1 as a new target for prevention and treatment of stress AGML, and also provide perioperative stress response. Through the duplication of WIRS ulcer model, we can better understand the pathogenesis of AGML, and provide new ideas for clinical prevention and treatment of severe burns, surgery and high AGML in critically ill patients.
research objective
The role of TRPV1 in stress-induced acute gastric mucosal injury was investigated by replicating the classical immersion restraint stress model. Sufentanil was used to verify the relationship between TRPV1 mRNA and mu-opioid receptor agonists in central and peripheral layers. SOD and MD in gastric mucosa and serum during stress-induced AGML in rats were detected. To investigate the relationship between TRPV1 mRNA and ASIC3 mRNA in gastric mucosa and the changes of oxidative and antioxidant capacity of the organism during water immersion restraint stress.
Experimental method
(1) 30 adult male SPF Wistar rats were randomly divided into three groups: normal group (NC group), immersion restraint stress group (WIRS group) and sufentanil pre-administration group (SF group). The experimental contents include: 1. After anesthesia, the gastric mucosa was scraped, the hypothalamus liquid nitrogen was frozen, the total RNA was extracted, and the expression of TRPV1 mRNA in gastric mucosa and hypothalamus was detected by real-time fluorescence quantitative PCR; 2. After gastric juice was removed, the gastric contents were washed out and observed under microscope. Gastric mucosal injury was observed, ulcer index (UI) was counted, gastric juice pH was measured, and the effect of sufentanil on stress-induced acute gastric mucosal lesion in rats was observed. Fourth, after anesthesia, abdominal aorta blood of rats in each group was taken, centrifuged and serum was taken. The concentration of MDA protein in gastric mucosa was determined to detect the content of SOD and MDA in tissues and serum of rats in each group.
(2) Twelve adult male SPF Wistar rats were randomly divided into three groups: normal group (NC group), immersion restraint stress group (WIRS group) and sufentanil pretreatment group (SF group). The location and expression of TRPV1 in gastric tissue were observed by immunohistochemistry.
(3) Forty adult male SPF Wistar rats were randomly divided into four groups: normal group (NC group), immersion restraint stress 2 h group (WIRS 2 h group), immersion restraint stress 4 h group (WIRS 4 h group) and immersion restraint stress 6 h group (WIRS 6 h group). The contents included: 1. After anesthesia, the rats in each group were scraped out for gastric mucosa nitrogen cryopreservation, and the total RNA was extracted by real-time fluorescence assay. The expression of TRPV1 mRNA and ASIC3 mRNA in gastric mucosa was detected by quantitative PCR at different time of immersion restraint stress; 2 gastric contents were washed and gastric mucosal lesions were observed under microscope and ulcer index (UI) was counted; 3 gastric tissue lesions in each group were markedly cut off with 0.2 *0.1 cm tissue mass, fixed with neutral formalin solution, and used. HE staining method was used to observe the changes of gastric tissue morphology in rats under water immersion restraint stress at different time points.
experimental result
(1) In NC group, a small amount of brown-gray food residue was found in the gastric cavity, and the gastric juice was transparent and yellowish. After washing, the gastric mucosa was smooth and intact, pale red, edema and bleeding were not found. In WIRS group, a large number of reddish-brown contents and hematogenous effusion were found in the gastric cavity. After washing, the gastric mucosa was evidently edematous, accompanied by punctate, corded bleeding, erosion and even ulcer. The contents of gastric cavity in pretreatment group were brown, the mucus of gastric mucosa thickened, occasional dot-like and linear bleeding spots were found, and the injury was significantly less than that in WIRS group. The ulcer index of gastric mucosal injury in rats was significantly increased after 6 hours of immersion restraint stress (P 0.05), and the UI was significantly decreased by sufentanil (P 0.05), but it was still higher than that in normal group. The pH value of gastric juice in RS group was significantly lower than that in normal group (P The results of fluorescence quantitative PCR showed that the relative expression of TRPV1 mRNA in gastric mucosa of stress group was (0.2 6550 The relative expression of TRPV1 mRNA in normal group was 3.2 (+ 0.8) times as much as that in normal group, and the difference was statistically significant (P 0.05).
(2) The results of immunohistochemistry showed that the expression of TRPV1 receptor was positive in brown granules. The structure showed that the expression of TRPV1 receptor in gastric tissue of immersion restraint stress group was slightly higher than that of normal group, while the expression of TRPV1 receptor in sufentanil pretreatment group was significantly higher than that of stress group and normal group (P 0.05).
(3) Fluorescence quantitative PCR showed that TRPV1 mRNA in gastric mucosa did not change significantly at WIRS 2H and WIRS 4h, but decreased significantly at WIRS 6h (P 0.05); ASIC3 mRNA relative expression increased significantly at the initial stage of stress (P 0.05) compared with NC group, WIRS 2h, WIRS 4H and WIRS 6h, ASIC3 mRNA decreased significantly at WIRS 6h (P 0.05). The gastric contents of rats in WIRS2h and WIRS4h groups were brown and occasionally bleeding spots and erosion were observed. The degree of bleeding spots and stripe ulcers in WIRS2h group was less than that in WIRS4h group. The ulcer index increased at 2 hours, 4 hours and 6 hours (13.00.24 vs 0.00.00, 16.40.05 vs 0.00.00, 30.40.41 vs 0.00.00, 30.40.41 vs 0.00.00.00, P 0.05), significantly higher than that of NC group. The activity of SOD in serum increased first and then decreased during stress. The highest level of MDA was detected at 4 hours of WIRS, and the lowest level was detected at 4 hours of WIRS. The relative expression of TRPV1 mRNA in gastric mucosa of WIRS 2h, WIRS 4H and WIRS 6h groups was (1.43 (0.19)), (1.20 (0.13) and (0.19 (0.03) times higher than that of NC group, respectively. The expression of TRPV1mRNA in group RS6h decreased, and the difference was statistically significant (P0.05).
empirical conclusion
(1) Sufentanil can effectively alleviate WIRS-induced acute gastric mucosal injury. The mechanism may be related to the control of oxidative stress, the decrease of gastric acid secretion and the regulation of TRPV1 mRNA expression in the central and peripheral regions.
(2) There is a compensatory process in the process of stress ulcer. The levels of serum SOD and MDA can be used as an early indicator to detect stress ulcer, and provide the basis for choosing the appropriate time to intervene in stress ulcer.
(3) TRPV1 and ASIC3 play a certain role in the process of stress-induced acute gastric mucosal lesion, and the change trend of them is consistent. ASIC3 is more sensitive to WIRS-induced acute gastric mucosal lesion than TRPV1.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R614

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 韓琴;;TRP通道參與溫度感覺的分子機(jī)制[J];成都醫(yī)學(xué)院學(xué)報(bào);2009年03期

2 劉鯤鵬;廖旭;薛富善;;舒芬太尼的藥理學(xué)和臨床應(yīng)用[J];中國(guó)醫(yī)藥導(dǎo)刊;2005年06期

3 蔣群;屠偉峰;;舒芬太尼預(yù)處理對(duì)大鼠急性胃粘膜病變的保護(hù)作用及與酸敏感離子通道的關(guān)系[J];南方醫(yī)科大學(xué)學(xué)報(bào);2010年05期

4 張穎;建全;王秋鵑;;酸感受離子通道亞基3的研究進(jìn)展[J];國(guó)外醫(yī)學(xué).藥學(xué)分冊(cè);2006年01期

5 楊龍貴;;應(yīng)激性潰瘍研究進(jìn)展[J];實(shí)用兒科臨床雜志;2010年19期

6 李魁君;李春剛;劉興君;;辣椒素受體(TRPV1)的生物學(xué)作用及其作為藥物靶點(diǎn)的研究進(jìn)展[J];沈陽藥科大學(xué)學(xué)報(bào);2011年11期

7 張?jiān)伱?張建福;閆長(zhǎng)棟;;辣椒素敏感傳入神經(jīng)在電刺激室旁核減輕大鼠胃缺血-再灌注損傷中的作用[J];世界華人消化雜志;2008年32期

8 王樂;王蘭蘭;曹宇;;TRPV1對(duì)LPS致熱大鼠體溫及下丘腦中Ca~(2+)濃度和cAMP含量的影響[J];中國(guó)藥理學(xué)通報(bào);2009年01期

9 王天懿;朱玉群;楊昭徐;;氧自由基和細(xì)胞凋亡在大鼠應(yīng)激性潰瘍中的作用[J];中國(guó)臨床營(yíng)養(yǎng)雜志;2008年05期

10 楊君;解建;;應(yīng)激性潰瘍的發(fā)病機(jī)制研究進(jìn)展[J];中國(guó)急救醫(yī)學(xué);2007年11期

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