神经肽Y双侧室旁核显微注射在瘦素调节2型糖尿病大鼠交感神经活性和压力反射功能中的作用
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摘要
目的观察神经肽Y(NPY)双侧室旁核显微注射在瘦素(LPN)调节2型糖尿病大鼠交感神经活性(SNA)和压力反射功能中的作用。方法将20只SD大鼠给以高糖高脂饲料喂养建立2型糖尿病模型;依据双侧室旁核显微注射人工脑脊液(aCSF)和NPY受体激动剂NPYx将建模成功的18只大鼠随机分为PVN-aCSF组和PVN-NPYx组,每组9只。分别测定两组SNA、平均动脉压(MAP)、心率(HR)基础数值,绘制对照压力感受性反射曲线;分别对两组大鼠各进行侧脑室LPN输注,1 h后(T_1)绘制压力感受性反射曲线;继续输注LPN的同时,PVN-aCSF组和PVN-NPYx组分别在双侧室旁核显微注射aCSF和NPYx,注射10 min后(T_2)绘制压力感受性反射曲线;比较两组各时点SNA、MAP、HR及SNA压力反射曲线中的最大值(Max)、最小值(Min)和取中值时的血压(BP_(50))。结果与本组基础时相比,PVN-aCSF组T1、T2时SNA、MAP、HR升高,PVN-NPYx组T_1时SNA、MAP、HR升高(P均<0.05);与本组T_1时比较,PVN-aCSF组T2时SNA、HR升高(P均<0.05);与PVN-aCSF组T_2时比较,PVN-NPYx组SNA、HR降低(P均<0.05)。与本组基础时相比,两组交感神经压力反射功能参数SNA的Max、Min及BP_(50)升高(P均<0.05);与本组T_1时比较,PVN-aCSF组T_2时Max、Min升高(P均<0.05);与PVN-aCSF组T_2时比较,PVN-NPYx组Max、Min降低(P均<0.05)。结论 NPY双侧室旁核显微注射可逆转LPN增加2型糖尿病大鼠SNA的作用,减弱LPN增强2型糖尿病大鼠压力感受性反射功能的作用。
Objective To observe the effect of microinjection of neuropeptide Y(NPY) into bilateral paraventricular nucleus on the regulation of sympathetic nerve activity(SNA) and baroreflex function in type 2 diabetic rats by leptin(LPN).Methods Twenty SD rats were fed with high-sugar and high-fat diet to establish the models of type 2 diabetes mellitus. According to the microinjection of artificial cerebrospinal fluid(aCSF) and NPY receptor agonist NPYx into the bilateral paraventricular nucleus, they were randomly divided into PVN-aCSF group and PVN-NPYx group, with 9 rats in each group. The basal values of SNA, mean arterial pressure(MAP) and heart rate(HR) were measured and the baroreflex curves were drawn. LPN was infused into lateral ventricles of the two groups, and baroreflex curves were drawn 1 hour later(T_1). With the continuous infusion of LPN, aCSF and NPYx were injected into the bilateral paraventricular nucleus in the PVN-aCSF group and PVN-NPYx group, respectively, and baroreceptive reflex curve was drawn 10 minutes after injection(T_2). SNA, MAP, HR, Max, Min, and BP_(50) were compared between the two groups at each time point. Results Compared with the baseline time, SNA, MAP and HR increased at T_1 and T_2 in the PVN-aCSF group, and increased at T_1 in the PVN-NPYx group(all P<0.05); compared with T_1 in the PVN-aCSF group, SNA and HR increased at T_2 in the PVN-aCSF group(all P<0.05); compared with T_2 in the PVN-aCSF group, SNA and HR decreased in the PVN-NPYx group(both P<0.05). Max, Min, and BP_(50) of sympathetic baroreflex function parameters increased in both groups compared with those at the baseline time(all P<0.05); Max and Min increased at T_2 in PVN-aCSF group compared with those at T_1(both P<0.05), and decreased at T_2 in the PVN-aCSF group(both P<0.05). Conclusion Microinjection of NPY into the bilateral paraventricular nucleus can reverse the effect of LPN in increasing SNA of type 2 diabetic rats, and weaken the effect of LPN in enhancing baroreflex function of type 2 diabetic rats.
Objective To observe the effect of microinjection of neuropeptide Y(NPY) into bilateral paraventricular nucleus on the regulation of sympathetic nerve activity(SNA) and baroreflex function in type 2 diabetic rats by leptin(LPN).Methods Twenty SD rats were fed with high-sugar and high-fat diet to establish the models of type 2 diabetes mellitus. According to the microinjection of artificial cerebrospinal fluid(aCSF) and NPY receptor agonist NPYx into the bilateral paraventricular nucleus, they were randomly divided into PVN-aCSF group and PVN-NPYx group, with 9 rats in each group. The basal values of SNA, mean arterial pressure(MAP) and heart rate(HR) were measured and the baroreflex curves were drawn. LPN was infused into lateral ventricles of the two groups, and baroreflex curves were drawn 1 hour later(T_1). With the continuous infusion of LPN, aCSF and NPYx were injected into the bilateral paraventricular nucleus in the PVN-aCSF group and PVN-NPYx group, respectively, and baroreceptive reflex curve was drawn 10 minutes after injection(T_2). SNA, MAP, HR, Max, Min, and BP_(50) were compared between the two groups at each time point. Results Compared with the baseline time, SNA, MAP and HR increased at T_1 and T_2 in the PVN-aCSF group, and increased at T_1 in the PVN-NPYx group(all P<0.05); compared with T_1 in the PVN-aCSF group, SNA and HR increased at T_2 in the PVN-aCSF group(all P<0.05); compared with T_2 in the PVN-aCSF group, SNA and HR decreased in the PVN-NPYx group(both P<0.05). Max, Min, and BP_(50) of sympathetic baroreflex function parameters increased in both groups compared with those at the baseline time(all P<0.05); Max and Min increased at T_2 in PVN-aCSF group compared with those at T_1(both P<0.05), and decreased at T_2 in the PVN-aCSF group(both P<0.05). Conclusion Microinjection of NPY into the bilateral paraventricular nucleus can reverse the effect of LPN in increasing SNA of type 2 diabetic rats, and weaken the effect of LPN in enhancing baroreflex function of type 2 diabetic rats.
引文
[1] 马爽,李宝新,张云良,等.2型糖尿病合并不同分级高血压患者血清Giα-2、NGAL水平变化及意义[J].山东医药,2017,57(33):5-8.
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[13] Prodel E, Barbosa TC, Mansur DE, et al. Effects of face cooling on pulse waveform and sympathetic activity in hypertensive subjects[J]. Clin Auton Res, 2017,27(1):45-49.
[14] 刘付贞,陈景福,潘德茂,等.柚皮苷通过抑制瘦素通路对抗高糖引起的心肌细胞损伤[J].中国病理生理杂志,2014,30(3):423-429.
[15] 陈岳林,王涛,沈粤春.瘦素在高血压发病机制中的作用[J].中华高血压杂志,2015,28(9):822-827.
[16] 朱冰,曲伸.瘦素调节糖代谢的机制研究进展[J].中国糖尿病杂志,2016,24(11):1040-1043.
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[19] Shi Z, Madden CJ, Brooks VL. Arcuate neuropeptide Y inhibits sympathetic nerve activity via multiple neuropathways[J]. J Clin Invest, 2017,127(7):2868-2880.
[20] Wang J, Yi J, Siegel PB, et al. Stress-induced suppression of neuropeptide Y-induced hunger in anorexic chicks involves corticotrophin-releasing factor signalling and the paraventricular nucleus of the hypothalamus[J]. J Neuroendocrinol, 2017,29(12).
[21] Yam KY, Ruigrok SR, Ziko I, et al. Ghrelin and hypothalamic NPY/AgRP expression in mice are affected by chronic early-life stress exposure in a sex-specific manner[J]. Psychoneuroendocrinology, 2017,86(7):73-77.
[22] 杨新玲,李杰,卢素玉,等.瘦素-下丘脑神经肽Y轴在2型糖尿病大鼠发病过程中的变化[J].中国全科医学,2014,17(36):4329-4332.
[23] 李宝新,张云良,王君,等.瘦素对2型糖尿病大鼠下丘脑神经肽Y水平的调节[J].中国卫生标准管理,2016,7(7):198-200.
[24] Adlan AM, Paton JF, Lip GY, et al. Increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity in rheumatoid arthritis[J]. J Physiol, 2017,595(3):967-981.
[25] Gordin D, Fem FE, Andersson B, et al. The effects of baroreflex activation therapy on blood pressure and sympathetic function in patients with refractory hypertension:the rationale and design of the Nordic BAT study[J]. Blood Press, 2017,26(5):294-302.
[26] de Faria AP, Ritter AM, Sabbatini AR, et al. Effects of leptin and leptin receptor SNPs on clinical-and metabolic-related traits in apparent treatment-resistant hypertension[J]. Blood Press, 2017,26(2):1-7.
[27] 李宝新,张云良,王君,等.糖尿病合并高血压大鼠瘦素和神经肽Y水平变化[J].中国循证心血管医学杂志,2016,8(9):1040-1042.
[28] 徐志伟,王文栋,常晓彤.胰岛素抵抗小鼠血清微小RNA的芯片及信息学分析[J].中国病理生理杂志,2016,32(4):738-744.
[2] Grassi G, Mark A, Esler M. The sympathetic nervous system alterations in human hypertension[J]. Circ Res, 2015,116(6):976-990.
[3] Yagishita Y, Uruno A, Fukutomi T, et al. Nrf2 Improves Leptin and Insulin Resistance Provoked by Hypothalamic Oxidative Stress[J]. Cell Rep, 2017,18(8):2030-2044.
[4] Gmc R, Tousoulis D, Mcfadden E, et al. Effects of neuropeptide Y on coronary artery vasomotion in patients with microvascular angina[J]. Int J Cardiol, 2017,238(4):123-127.
[5] Chu SC, Chen PN, Chen JR, et al. Role of hypothalamic leptin-LepRb signaling in NPY-CART-mediated appetite suppression in amphetamine-treated rats[J]. Horm Behav, 2018,98(3):173-182.
[6] Shi YC, Lau J, Lin Z, et al. Arcuate NPY controls sympathetic output and BAT function via a relay of tyrosine hydroxylase neurons in the PVN[J]. Cell Metab, 2013,17(2):236-248.
[7] 练飞鸿,饶芳,邝素娟,等.2型糖尿病大鼠心功能变化及RAGE表达增强和钙调控异常[J].中国病理生理杂志,2018,34(3):488-493.
[8] Cassaglia PA, Shi Z, Brooks VL. Insulin increases sympathetic nerve activity in part by suppression of tonic inhibitory neuropeptide Y inputs into the paraventricular nucleus in female rats[J]. Am J Physiol Regul Integr Comp Physiol, 2016,311(1):R97-R103.
[9] 余舒杰,周彬,宋志明,等.高血压和高血压合并糖尿病患者血浆可溶性VEGFR2与SOD水平的变化[J].中国病理生理杂志,2015,31(5):797-801.
[10] Pérez-Pérez A, Vilarino-García T, Fernández-Riejos P, et al. Role of leptin as a link between metabolism and the immune system[J]. Cytokine Growth Factor Rev, 2017,35(3):71-84.
[11] Su Y, Foppen E, Fliers E, et al. Effects of Intracerebroventricular Administration of Neuropeptide Y on Metabolic Gene Expression and Energy Metabolism in Male Rats[J]. Endocrinology, 2016,157(8):3070-3085.
[12] Straznicky NE, Grima MT, Sari CI, et al. Comparable Attenuation of Sympathetic Nervous System Activity in Obese Subjects with Normal Glucose Tolerance, Impaired Glucose Tolerance, and Treatment Naive Type 2 Diabetes following Equivalent Weight Loss[J]. Front Physiol, 2016,3(7):516.
[13] Prodel E, Barbosa TC, Mansur DE, et al. Effects of face cooling on pulse waveform and sympathetic activity in hypertensive subjects[J]. Clin Auton Res, 2017,27(1):45-49.
[14] 刘付贞,陈景福,潘德茂,等.柚皮苷通过抑制瘦素通路对抗高糖引起的心肌细胞损伤[J].中国病理生理杂志,2014,30(3):423-429.
[15] 陈岳林,王涛,沈粤春.瘦素在高血压发病机制中的作用[J].中华高血压杂志,2015,28(9):822-827.
[16] 朱冰,曲伸.瘦素调节糖代谢的机制研究进展[J].中国糖尿病杂志,2016,24(11):1040-1043.
[17] Zhu P, Sun W, Zhang C, et al. The role of neuropeptide Y in the pathophysiology of atherosclerotic cardiovascular disease[J]. Int J Cardiol, 2016,220:235-241.
[18] Yi M, Li H, Wu Z, et al. A Promising Therapeutic Target for Metabolic Diseases: Neuropeptide Y Receptors in Humans[J]. Cell Physiol Biochem, 2017,45(1):88-107.
[19] Shi Z, Madden CJ, Brooks VL. Arcuate neuropeptide Y inhibits sympathetic nerve activity via multiple neuropathways[J]. J Clin Invest, 2017,127(7):2868-2880.
[20] Wang J, Yi J, Siegel PB, et al. Stress-induced suppression of neuropeptide Y-induced hunger in anorexic chicks involves corticotrophin-releasing factor signalling and the paraventricular nucleus of the hypothalamus[J]. J Neuroendocrinol, 2017,29(12).
[21] Yam KY, Ruigrok SR, Ziko I, et al. Ghrelin and hypothalamic NPY/AgRP expression in mice are affected by chronic early-life stress exposure in a sex-specific manner[J]. Psychoneuroendocrinology, 2017,86(7):73-77.
[22] 杨新玲,李杰,卢素玉,等.瘦素-下丘脑神经肽Y轴在2型糖尿病大鼠发病过程中的变化[J].中国全科医学,2014,17(36):4329-4332.
[23] 李宝新,张云良,王君,等.瘦素对2型糖尿病大鼠下丘脑神经肽Y水平的调节[J].中国卫生标准管理,2016,7(7):198-200.
[24] Adlan AM, Paton JF, Lip GY, et al. Increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity in rheumatoid arthritis[J]. J Physiol, 2017,595(3):967-981.
[25] Gordin D, Fem FE, Andersson B, et al. The effects of baroreflex activation therapy on blood pressure and sympathetic function in patients with refractory hypertension:the rationale and design of the Nordic BAT study[J]. Blood Press, 2017,26(5):294-302.
[26] de Faria AP, Ritter AM, Sabbatini AR, et al. Effects of leptin and leptin receptor SNPs on clinical-and metabolic-related traits in apparent treatment-resistant hypertension[J]. Blood Press, 2017,26(2):1-7.
[27] 李宝新,张云良,王君,等.糖尿病合并高血压大鼠瘦素和神经肽Y水平变化[J].中国循证心血管医学杂志,2016,8(9):1040-1042.
[28] 徐志伟,王文栋,常晓彤.胰岛素抵抗小鼠血清微小RNA的芯片及信息学分析[J].中国病理生理杂志,2016,32(4):738-744.