本文選題：糖尿病神經(jīng)病變 + 心肌缺血再灌注��； 參考：《山西醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:通過分析降鈣素基因相關(guān)肽(CGRP)、P物質(zhì)(SP)在心肌,背根神經(jīng)節(jié)及血清的表達變化與糖尿病大鼠痛覺減退、心肌易損性增加的關(guān)系,探討痛覺減退與糖尿病大鼠心肌缺血再灌注損傷易損性增加的相關(guān)性。方法:1、Ⅰ型糖尿病大鼠模型的建立:200-250g雄性SD大鼠60只,腹腔注射鏈脲佐菌素(streptozocin,STZ,50mg/kg)作為糖尿病組(DM組)。將注射STZ后一周內(nèi)血糖持續(xù)16.7mmol/L為糖尿病造模成功標(biāo)準(zhǔn);同時喂養(yǎng)30只同周齡的正常大鼠作為對照,每周測量體重、血糖值、熱痛甩尾潛伏期(tail flick latency,TFL);注射STZ第五周末采用ELISA法測定兩組大鼠血甘油三酯值并比較分析。2、測量甩尾潛伏期及糖尿病分組:根據(jù)注射STZ后第5周末測得TFL值是否大于注射STZ前對照值的2倍,將糖尿病大鼠進一步分為DM1組(TFL對照值x 2)和DM2組(TFL對照值x 2)。3、測量、分析兩組糖尿病大鼠CGRP、SP變化:采用免疫熒光技術(shù)和和ELISA法測定心肌、上胸段(T1-5)和腰骶背根神經(jīng)節(jié)(DRG)及血清CGRP,SP的含量:并觀察其在心肌處的含量分布。分析DM1組和DM2組上述測量值差異。4、心肌梗死面積及心肌細胞凋亡的分析:采用TTC染色法、TUNEL分析凋亡試劑盒測定分析心肌梗死面積及心肌細胞凋亡程度,并分析DM1組和DM2組上述測量值差異。5、測量、分析糖尿病大鼠神經(jīng)生長因子(NGF)及辣椒素受體(TRPV1):采用ELISA法和western blot法分別定量分析缺血心肌NGF及TRPV1的表達變化。結(jié)果:1、糖尿病組大鼠造模五周后,與對照組相比,體重發(fā)生顯著降低降低(P0.01),而血糖在造模早期即升高至糖尿病水平(24h后),且甘油三酯亦出現(xiàn)顯著升高。2、糖尿病組大鼠甩尾潛伏期逐漸延長,至5w時有顯著性差異。與對照組相比,DM組的CGRP、SP在心肌、背根神經(jīng)節(jié)及血清處的含量均顯著下降(P0.05),且DM2組中CGRP、SP含量顯著低于DM1組水平(P0.05)。3、與I/R組正常大鼠相比,I/R組糖尿病大鼠心肌梗死面積顯著增加、心肌細胞凋亡比率均顯著升高(P0.05);DM組中,DM2組大鼠心肌缺血再灌注后,各項心肌損傷指標(biāo)均顯著高于DM1組。與相應(yīng)的假手術(shù)組比較,I/R組正常大鼠CGRP,SP顯著升高,I/R組糖尿病大鼠CGRP,SP升高不顯著。4、與相應(yīng)的假手術(shù)組比較,正常大鼠I/R組缺血心肌處TRPV1表達顯著升高(P0.05),糖尿病I/R組TRPV1表達變化不顯著,并且顯著低于非糖尿病組(P0.05),且DM1組和DM2組相比,缺血心肌處TRPV1表達無顯著差異。各組NGF含量變化:與相應(yīng)的假手術(shù)組比較,正常I/R組背根神經(jīng)節(jié)、缺血心肌及血清表達顯著升高(P0.05),糖尿病I/R組NGF表達變化不顯著;與對照組相比,DM1組NGF含量顯著升高(P均0.05),而DM2組NGF含量顯著下降(P0.05)。結(jié)論:1、糖尿病組大鼠在注射STZ后痛覺逐漸減退,表現(xiàn)為甩尾潛伏期持續(xù)升高,而正常組大鼠甩尾潛伏期無顯著改變;糖尿病大鼠個體甩尾潛伏期變化率不同,反映其外周和內(nèi)臟感覺神經(jīng)病變程度不同,并且與感覺神經(jīng)CGRP,SP顯著降低程度相關(guān)。2、甩尾潛伏期變化率較高的DM組大鼠(DM2組)對心肌缺血再灌注損傷更敏感,推斷這可能與DM2組CGRP,SP含量與DM1組相比顯著下降有關(guān)。3、糖尿病大鼠NGF和TRPV1的變化可能與感覺神經(jīng)病變及CGRP、SP含量變化有關(guān)。
[Abstract]:Objective: To investigate the relationship between the changes of the expression of calcitonin gene related peptide (CGRP), substance P (SP) in the myocardium, the dorsal root ganglion and serum, the relationship between the decrease of pain and the increase of myocardial vulnerability in diabetic rats, and to explore the correlation between the decrease of pain and the increase of vulnerability of myocardial ischemia reperfusion injury in diabetic rats. Methods: 1, model type I diabetic rat model Establishment: 60 200-250g male SD rats, intraperitoneal injection of streptozotocin (streptozocin, STZ, 50mg/kg) as diabetic group (group DM). The blood glucose sustained 16.7mmol/L in the week after STZ was used as a successful standard for diabetes modeling. At the same time, 30 normal rats of the same age were fed as control, and the weight, blood sugar, and tail flick incubation period were measured weekly. Tail flick latency, TFL); the blood triglyceride value of two groups of rats was measured by ELISA method at the end of the injection of STZ and the.2 was compared and analyzed, and the latency of tail flick and diabetes group were measured. The diabetic rats were further divided into DM1 group (TFL control 2) and 2 groups according to whether the TFL values were more than 2 times of the control value before the injection of STZ fifth weekend after the injection of STZ. (TFL control value x 2).3, measurement and analysis of CGRP, SP changes in two groups of diabetic rats: Determination of myocardium by immunofluorescence and ELISA and the content of CGRP and SP in the upper thoracic segment (T1-5) and the lumbosacral dorsal root ganglion (DRG) and serum, and to observe the distribution of its content in the myocardium. The analysis of myocyte apoptosis: TTC staining and TUNEL analysis of apoptosis kits were used to determine the area of myocardial infarction and the degree of myocardial apoptosis, and the difference between the DM1 group and the DM2 group was analyzed. The measurement and analysis of the neural growth factor (NGF) and capsaicin receptor (TRPV1) in diabetic rats were measured by ELISA and Western blot respectively. The changes in the expression of NGF and TRPV1 in the ischemic myocardium were analyzed. Results: 1, after five weeks of modeling, the body weight of the diabetic rats decreased significantly (P0.01), and the blood sugar increased to the diabetes level in the early stage (after 24h), and the triglyceride also increased significantly in.2, and the tail flick latency of the diabetic rats was gradually prolonged, to 5W. Compared with the control group, the content of CGRP and SP in the DM group was significantly decreased in the myocardium, the dorsal root ganglion and the serum level (P0.05), and the CGRP, SP content in the DM2 group was significantly lower than that of the DM1 group (P0.05).3. Compared with the I/R group, the infarct area of the cardiac muscle in the I/R group diabetic rats increased significantly, and the ratio of cardiomyocyte apoptosis was significantly increased. In group DM, the myocardial injury indexes of group DM2 rats were significantly higher than those in group DM1. Compared with the corresponding sham operation group, the normal rats in group I/R were significantly increased in SP, CGRP in group I/R, and the increase of SP was not significantly.4. Compared with the corresponding sham operation group, the expression of ischemic myocardium in the normal rats was significant. There was no significant change in TRPV1 expression in diabetic group I/R (P0.05), and significantly lower than that in non diabetic group (P0.05), and there was no significant difference in the expression of TRPV1 in the ischemic myocardium between the DM1 group and the DM2 group. The changes of NGF content in each group were compared with the corresponding sham operation group, the normal I/R group dorsal root ganglion, the ischemic myocardium and the serum expression were significantly increased (P0.05), diabetes mellitus (P0.05), diabetes mellitus (P0.05), diabetes mellitus The expression of NGF in the I/R group was not significant. Compared with the control group, the NGF content in the DM1 group increased significantly (P 0.05), while the NGF content in the DM2 group decreased significantly (P0.05). Conclusion: 1, the diabetic rats were gradually decreasing after the injection of STZ, showing a continuous increase in the tail flick latency, but there was no significant change in the tail flick latency of the normal group; the individual diabetic rats were not significantly changed. The change rate of the tail flick incubation period was different, reflecting the different degree of peripheral and visceral sensory neuropathy, and associated with the significant reduction of the sensory nerve CGRP, SP,.2. The DM group (DM2 group) with higher tail flick latency (DM2 group) was more sensitive to myocardial ischemia reperfusion injury. It was concluded that this may be significantly lower than the DM2 group CGRP, SP content compared with the DM1 group. The changes of NGF and TRPV1 in diabetic rats may be related to the changes of sensory neuropathy and the contents of CGRP and SP in.3.
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R587.2

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本文編號：1990457