Effect of amitriptyline on gastrointestinal function and brain-gut peptides: A double-blind trial

AIM: To study the effects of low-dose amitriptyline (AMT) on gastrointestinal function and brain-gut peptides in healthy Chinese volunteers. METHODS: This was a double-blind, randomised, placebo-controlled, two-period cross-over trial. Twentyeight healthy volunteers were randomised and administered 1-wk treatments of AMT (12.5 mg tid) or placebo. Before and during the final two days of treatment, gastric emptying, proximal gastric accommodation and visceral sensitivity were measured by drinkingultrasonography test; the orocecal transit time (OCTT) was measured by lactulose hydrogen breath test, and fasting blood was collected. Plasma levels of ghrelin, motilin and neuropeptide Y (NPY) were measured by enzyme-linked immunosorbent assay kits.RESULTS: AMT slowed the OCTT (109.2 ± 29.68 min vs 96.61 ± 23.9 min, P = 0.004) but did not affect liquid gastric emptying and had no effect on proximal gastric accommodation. AMT resulted in decreases in the visual analogue scale (VAS) for difficulty in drinking 600 and 800 mL of water (3.57 ± 0.94 vs 2.98 ± 0.85, 5.57 ± 0.82 vs 4.57 ± 0.98, P < 0.01 for both), although it had no significant effect on the VAS for difficulty in drinking 200 mL and 400 mL of water. AMT significantly increased the plasma ghrelin level (442.87 ± 176.79 pg/mL vs 526.87 ± 158.44 pg/mL, P = 0.04) and the neuropeptide-Y level (890.15 ± 131.46 pg/mL vs 965.64 ± 165.63 pg/mL, P = 0.03), whereas it had no effect on the MTL level. CONCLUSION: Low-dose AMT could slow OCTT, make the stomach less sensitive and increase the plasma levels of ghrelin and NPY. Thus, we recommend the use of low-dose AMT for functional gastrointestinal disorders.

Study on the regulation of brain-gut peptide by Shenling Baizhu San in functional diarrhea rats

Objective:To explore the therapeutic mechanism of Shenling Baizhu San (SLBZS) on functional diarrhea (FDr) by studying the brain-gut axis and related neuropeptides.Methods:Sixty male Wistar rats were randomly divided into the control group,model group,SLBZS-treated group and Montmorillonite Powder-treated group (MP-treated group) (n =15/group).Rats received gavage after the establishment of functional diarrhea.An equal volume of SLBZS solution and Montmorillonite Powder (MP) solution was administered to the SLBZS-treated group and MP-treated group,respectively,and an equal volume of distilled water was administered to the control group and the model group.The chemical components and targets related to SLBZS were identified from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID).The effective chemical components were screened based on oral bioavailability (OB) and drug like-index (DL),and their biological functions were analyzed by GlueGO.Based on this screening,the expression of Cholecystokinin (CCK) and Ghrelin in the hypothalamus of rats was detected by real-time PCR (RT-PCR) and western blotting.Results:In this study,72 effective components and 190 core targets of SLBZS were screened.SLBZS may regulate smooth muscle contraction,energy metabolism and other biological processes.The results of RT-PCR showed that in the model group,the expression of CCK mRNA (P =.001) and Ghrelin mRNA (P =.000) increased significantly.Compared with the model group,CCK mRNA (P =.007) and Ghrelin mRNA (P =.001) levels in SLBZS-treated rats were decreased significantly.The results of western blotting showed that in the model group,the protein expression of CCK (P =.001) and Ghrelin (P =.000) increased significantly.The protein levels of CCK (P =.001) and Ghrelin (P =.005) in the SLBZS-treated group were decreased significantly compared with the model group.Conclusion:SLBZS improved functional diarrhea by regulating the brain-gut axis.Changes in the expressions of brain-gut peptide,CCK and Ghrelin might explain the pathogenesis of functional diarrhea related to brain-gut peptide and gastrointestinal hormone.

Gastric motor effects of ghrelin and growth hormone releasing peptide 6 in diabetic mice with gastroparesis

AIM:To investigate the potential therapeutic significance of ghrelin and growth hormone releasing peptide 6 (GHRP-6) in diabetic mice with gastric motility disorders. METHODS: A diabetic mouse model was established by intraperitoneal (ip) injection of alloxan. Diabetic mice were injected ip with ghrelin or GHRP-6 (20-200 μg/kg), and the effects on gastric emptying were measured after intragastric application of phenol red. The effect of atropine, NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) or D-Lys3-GHRP-6 (a growth hormone secretagogue receptor (GHS-R) antagonist) on the gastroprokinetic effect of ghrelin or GHRP-6 (100 μg/kg) was also investigated. The effects of ghrelin or GHRP-6 (0.01-10 μmol/L) on spontaneous or carbachol-induced contractile amplitude were also investigated in vitro, in gastric fundic circular strips taken from diabetic mice. The presence of growth hormone secretagogue receptor 1a transcripts in the fundic strips of diabetic mice was detected by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: We established a diabetic mouse model with delayed gastric emptying. Ghrelin and GHRP-6 accelerated gastric emptying in diabetic mice with gastroparesis. In the presence of atropine or L-NAME, which delayed gastric emptying, ghrelin and GHRP-6 (100 μg/kg) failed to accelerate gastric emptying. D-Lys3-GHRP-6 also delayed gastric emptying induced by the GHS-R agonist. Ghrelin and GHRP-6 increased the carbachol-induced contractile amplitude in gastric fundicstrips taken from diabetic mice. RT-PCR confirmed the presence of GHS-R mRNA in the strip preparations. CONCLUSION: Ghrelin and GHRP-6 increase gastric emptying in diabetic mice with gastroparesis, perhaps by activating peripheral cholinergic pathways in the enteric nervous system.

Therapeutic effect of zhuodu theory on ulcerative colitis and its effect on brain-gut peptide in serum and inflammatory factor

Objective:To investigate the therapeutic effect of traditional Chinese medicine xiezhuojiedu decoction on ulcerative colitis(UC)based on zhuodu theory and its effect on serum brain-gut peptide and inflammatory factors.Methods:110 cases of UC patients were divided into 2 groups according to the random number table method,with 55 cases in each group.The control group was treated with mesalazine,and the treatment group was given oral administration of Chinese medicine xiezhuojiedu decoction on the basis of the control group.Both groups received continuous treatment for 8 weeks.Integral of TCM syndromes,serum inflammatory factor and brain-gut peptide before and after treatment were compared between the two groups.The clinical efficiency,mucosal healing rate and endoscopic response rate of the two groups were compared.Results:After treatment,Integral of the main TCM syndromes abdominal pain,diarrhea,abdominal distention,mucous hematochezia,tenesmus of the treatment group were lower than the control group(P<0.01),the levels of serum(Tumor necrosis factor-α,(TNF-α),Interleukin(IL)-33,Substance P(SP)were lower than the control group(P<0.01),the levels of IL-10,vasoactive intestinal peptide(VIP),Somatostatin(SS)were higher than the control group(P<0.01),the clinical efficiency and mucosal healing rate were higher than control group(P<0.05),The difference was statistically significant.Conclusion:Based on the zhuodu theory,the xiezhuojiedu decoction can effectively regulate the levels of inflammatory factor and brain-gut peptide in the treatment of UC,improve the symptoms of patients,and promote the repair of intestinal mucosa.It's effective in treatment.

Effects of vagus nerve preservation and vagotomy on peptide YY and body weight after subtotal gastrectomy

AIM:To investigate the relationship between the function of vagus nerve and peptide YY 3-36 and ghrelin levels after subtotal gastrectomy.METHODS:We enrolled a total of 16 patients who underwent subtotal gastrectomy due to gastric cancer.All surgeries were performed by a single skilled surgeon.We measured peptide YY 3-36,ghrelin,leptin,insulin,growth hormone levels,and body weight immediately before and one month after surgery.RESULTS:Vagus nerve preservation group showed less body weight loss and less increase of peptide YY 3-36 compared with vagotomy group(-5.56 ± 2.24 kg vs-7.85 ± 1.57 kg,P = 0.037 and 0.06 ± 0.08 ng/mL vs 0.19 ± 0.12 ng/mL,P = 0.021,respectively).Moreover,patients with body weight loss of less than 10% exhibited reduced elevation of peptide YY 3-36 level,typically less than 20% [6(66.7%) vs 0(0.0%),P = 0.011,odd ratio = 3.333,95% confidence interval(1.293,8.591)].CONCLUSION:Vagus nerve preservation contributes to the maintenance of body weight after gastrectomy,and this phenomenon may be related to the suppressed activity of peptide YY 3-36.

Effects of Pyridoxine on Selected Appetite Regulating Peptides mRNA Expression in Hypothalamic PVN/ARC Nuclei and Gastrointestinal Tract Tissues

An experiment was conducted to investigate the effect of dietary pyridoxine on the gene expression of appetite-regulating peptides in the hypothalamus and gastrointestinal tract of rabbits. Thirty-two rabbits were randomly divided into 2 treatments for 8 weeks (16 replicates/group and 1 rabbit/replicate). The treatments were fed a basal diet (control, measured pyridoxine content is 4.51 mg/kg) and the basal diet with a pyridoxine supplementation at 10 mg/kg (pyridoxine, measured pyridoxine content is 14.64 mg/kg). The results showed that dietary pyridoxine did not significantly alter the mRNA levels of neuropeptide Y, agouti related peptide, pro-opiomelanocortin and cocaine, amphetamine regulated transcript, peptide YY and cholecystokinin in arcuate nucleus, peptide YY in jejunum and ileum, and cholecystokinin in duodenum, jejunum and ileum (P > 0.05). Compared with the control, the mRNA levels of corticotropin-releasing hormone and melanocortin 4 receptor in paraventricular nuclei and peptide YY in duodenum were significantly decreased after pyridoxine treatment (P 0.05). In conclusion, the appetite genes of melanocortin 4 receptor and corticotropin-releasing hormone in paraventricular nuclei and peptide YY in duodenum are involved in the pyridoxine-caused hyperphagia.

脑肠肽Obestalin与Ghrelin的研究进展

Obe statin与Ghrelin是两种重要的脑肠肽(brain-gut peptide,BGP),与其受体结合后发挥重要的生物学功能.Obestatin位于胃生长素前体原的76-98片段,可以结合孤儿G蛋白GPR39受体,抑制食物摄取、空肠的蠕动和体质量的增加.而Ghrelin则位于胃生长素前体原的24-51肽段,可以结合蛋白受体GHS-R,增加食欲和体质量,促进GH的释放,影响心血管功能和免疫机能等.Obestatin被认为是Ghrelin的生物学拮抗剂或阴阳活性多肽.

抑郁障碍对慢性收缩性心力衰竭患者sST2、NT-pro BNP和Ghrelin水平及预后的影响

目的探讨抑郁障碍对慢性收缩性心力衰竭患者血浆中分泌型ST2（sST2）和神经激素（NT—proBNP与Gh—relin）水平及其预后的影响。方法纳入射血分数≤40％，平均年龄（60±12）岁的146例心衰患者，分别接受医院焦虑抑郁量表（HADS）、汉密尔顿抑郁量表（HAMD）、汉密尔顿焦虑量表（HAMA）和明尼苏达心力衰竭生活质量量表（ML-HFQ）的评估，并测定血浆sST2、NT-proBNP和Ghrelin水平。所有患者随访9个月，初级终点是全因死亡和因心衰再次住院。结果与心衰无抑郁障碍组患者相比，心衰合并抑郁障碍的患者（52例，35．6％）血浆sST2水平（55．3ng／mL％41．1ng／mL，P％0．01）和NT—proBNP水平（5886pg／mL＂US．2682pg／mL，P％0．01）显著增高，而Ghrelin水平降低（7．0ng／mL7dS．7．9ng／mL，P=0．041）。sST2和NT—proBNP水平与抑郁障碍独立相关。9个月随访期间抑郁障碍组全因死亡率（32．7％VS．7．4％，P％0．01）和因心衰再住院率（48．1％ vs 27．7％，P〈0．01）显著高于无抑郁障碍组。多因素Cox回归分析显示在校正临床相关变量后抑郁障碍（HR2．24，95％ CI 1．18～4．25，P=0．014）仍是心衰患者全因死亡和心衰再住院的独立危险因素。伴抑郁障碍且sST2〉45．1ng／mL或NT—proBNP〉3286pg／mL的心衰患者全因死亡和心衰再住院的风险显著增加。结论心衰伴抑郁障碍的患者血浆sST2和NT—proBNP水平增高，Ghrelin水平降低。抑郁障碍联合sST2或NT-proBNP对心衰患者不良预后有较高的预测价值。

类风湿性关节炎患者血浆Ghrelin水平变化及其与血清CRP、RF、抗-CCP的关系

目的观察类风湿性关节炎(RA)患者血浆Ghrelin水平变化,并探讨其与血清C反应蛋白(CRP)、类风湿因子(RF)、抗环瓜氨酸肽抗体(抗-CCP)的关系。方法选取RA患者105例作为RA组,关节无变形(1级)39例,关节轻度变形(2级)45例,关节严重变形(3级)21例。健康体检者120例作为对照组。抽取两组空腹静脉血,采用酶联免疫吸附法检测血浆Ghrelin、抗-CCP水平,采用免疫比浊法检测C反应蛋白(CRP),采用透射比浊法检测类风湿因子(RF),采用魏氏法检测ESR,采用电阻抗法检测血小板(PLT)。结果 RA组血浆Ghrelin水平明显低于对照组(P<0.05);随着关节变形级别的增加,血浆Ghrelin水平逐渐降低,3级者<2级者<1级者(P均<0.05);RA组中,血浆Ghrelin水平与CRP、RF、抗抗-CCP呈明显负相关(r分别为-0.511、-0.302、-0.527,P均<0.05),对照组中血浆Ghrelin水平仅与CRP呈负相关(r=-0.221,P<0.05)。结论 RA患者血浆Ghrelin水平明显降低,Ghrelin水平与关节变形程度、CRP、RF、抗-CCP存在一定的相关性。

模拟失重对大鼠血浆ghrelin、VIP和胃肠动力的影响

目的探讨模拟失重状态下胃肠激素ghrelin和VIP的改变以及对胃肠动力的影响。方法 32只Wistar大鼠,随机分为4组,每组8只,按模拟失重的时程分为14 d组和21 d组,并分别设立非悬吊14 d对照组和非悬吊21 d对照组。先后进行胃浆膜肌电的描记、葡聚糖蓝2000标记法测定胃残留率和小肠推进率,血浆ghrelin和VIP浓度分别用酶免法(ELISA)和放免法(RI)测定。结果悬吊14 d组与21 d组与相应对照组比较,ghrelin浓度下降VIP浓度升高,同时表现为胃肌电延缓,胃残留率增加;小肠推进率下降,差异均具有统计学意义(P<0.05)。结论模拟失重状态下血浆ghrelin下降和VIP升高可能是导致胃肠动力下降的重要因素之一。

Ghrelin的研究进展

主要对Ghrelin的历史背景、结构与功能、受体的分布、生物学的作用及其前景展望作出详细的论述。

生长激素释放肽——ghrelin的研究进展

生长激素释放肽(ghrelin)是最近发现的一种新的多肽,它分布在许多组织如胃肠、垂体、下丘脑,淋巴组织等。它的生理作用包括调节垂体生长激素(growth hormone,GH)的释放,参与能量代谢,影响心血管功能和其他激素的释放。现在很多研究也发现ghrelin和肥胖、2型糖尿病、代谢综合征等疾病存在某种关联。本文主要讨论了ghrelin和此类疾病的关系。

Ghrelin与心力衰竭

Ghrelin是一种由28个氨基酸组成的多肽,是生长激素促分泌素受体的内源性配体。近年来研究显示心力衰竭时ghrelin及其受体的表达及功能发生变化;Ghrelin除具有促进生长激素分泌的作用外,还具有抑制心肌细胞凋亡、抑制心室重构、增强心肌收缩力、直接保护心肌、改善心肌能量代谢、改善心功能、延缓心源性恶病质的生物学效应。这就提示ghrelin可能从上述多方面发挥抗心力衰竭的作用,具有治疗心力衰竭的潜在功效。

ghrelin对海马神经干细胞糖氧剥夺性损伤的影响及机制

目的观察ghrelin对糖氧剥夺诱导海马神经干细胞损伤的影响,并探讨核受体辅阻遏子1(N-CoR1)/磷脂酰肌醇3-激酶(PI3K)通路在该影响中的作用。方法将细胞随机分为正常对照组、损伤模型组、ghrelin治疗组、GHRP组、LY294002组、siRNA空白对照组、N-CoR1 siRNA组。正常对照组在正常糖含量的培养基、正常氧含量混合气体的普通培养箱中培养24 h,其余各组细胞行糖氧剥夺处理,处理后培养条件同正常对照组。siRNA空白对照组、N-CoR1 siRNA组行糖氧剥夺处理前1 h,培养液更换为含等量转染溶剂Lipofectamine2000或N-CoR siRNA脂质体的培养液,持续转染至糖氧剥夺之后的24 h。ghrelin治疗组在糖氧剥夺处理结束后,将培养液更换为含ghrelin的培养基继续培养24 h。GHRP-6组、LY294002组在糖氧剥夺处理结束后,预先给予ghrelin受体拮抗剂D-Lys ^3-GHRP-6或PI3K抑制剂LY294002处理1 h,再同时给予ghrelin处理,继续培养24 h。收集各组细胞,采用CCK-8法检测海马神经干细胞增殖活力,Western blotting法检测N-CoR1、PI3K、增殖标志蛋白增殖细胞核抗原(PCNA)及凋亡标志蛋白Bax、Bcl-2。CCK-8实验中ghrelin治疗组ghrelin浓度分别为4、20、100 nmol/L,其余实验中ghrelin浓度均为100 nmol/L。结果与正常对照组比较,损伤模型组海马神经干细胞增殖活力降低,细胞PCNA表达减少、Bax/Bcl-2增大,N-CoR表达明显增多、PI3K表达减少(P均<0.01);与损伤模型组比较,ghrelin治疗组随ghrelin作用浓度增高细胞增殖活力增高(P均<0.01),细胞PCNA表达增多、Bax/Bcl-2减小,N-CoR表达减少、PI3K表达增多(P均<0.01);与ghrelin治疗组(100 nmol/L)比较,GHRP组、LY29400组神经干细胞增殖活力降低,PCNA表达减少、Bax/Bcl-2增大,N-CoR表达明显增多、PI3K表达减少(P均<0.01)。与siRNA空白对照组比较,N-CoR siRNA组神经干细胞增殖活力增高,N-CoR siRNA组PCNA表达增多、Bax/Bcl-2减小,N-CoR siRNA组N-CoR表达减少、PI3K表达增多(P均<0.01)。结论ghrelin可抑制糖氧剥夺诱导的海马神经干细胞损伤,其机制与调节N-CoR/PI3K信号通路有关。

消痞五穴针刺法配合中脘穴贴敷对三阴性乳腺癌化疗相关性消化不良患者胃电图和CGRP、Ghrelin和5-HT的影响

目的观察消痞五穴针刺法配合中脘穴贴敷对三阴性乳腺癌(TNBC)化疗相关性消化不良患者胃电图和降钙素基因相关肽(CGRP)、胃促生长素(Ghrelin)和5-羟色胺(5-HT)的影响。方法将2016年10月—2018年10月东莞市人民医院收治的129例TNBC化疗相关性消化不良患者随机分为观察组65例和对照组64例,对照组给予西医治疗,观察组在对照组治疗基础上给予消痞五穴针刺法配合中脘穴贴敷治疗,2组疗程均为4周。记录2组治疗前后中医症状积分、患者整体营养状况主观评估(PG-SGA)评分、胃电图及血清CGRP、Ghrelin、5-HT水平和生活质量的变化,并统计2组临床疗效。结果2组治疗后中医症状积分、PG-SGA评分均明显降低(P均<0.05),治疗后观察组中医症状积分、PG-SGA评分均低于对照组(P均<0.05)。2组治疗后餐前和餐后平均收缩波频率(MFC)、收缩波幅值(AC)、波形反应面积(WRA)及血清CGRP、Ghrelin、5-HT水平和乳腺癌患者生命质量测定量表(FACT-B)中文版中生理维度、附加关注、功能维度评分与总评分均明显增高(P均<0.05),治疗后观察组以上指标均明显高于对照组(P均<0.05)。观察组治疗总有效率为89.2%(58/65),显著高于对照组的70.3%(45/64),差异有统计学意义(P<0.05)。结论消痞五穴针刺法配合中脘穴贴敷可显著缓解TNBC化疗相关性消化不良患者的临床症状,改善机体营养状况,并调节胃动力学及胃肠激素水平,从而有利于生活质量的改善。

新诊断2型糖尿病患者血清BNP及Ghrelin水平与IR的关系及意义

目的:探讨新诊断2型糖尿病(T2DM)患者血清脑钠肽(BNP)与生长激素释放肽(Ghrelin)的表达水平及二者与胰岛素抵抗(IR)的关系。方法:选取新诊断T2DM患者40例作为2型糖尿病(T2DM)组,同期体检健康者40例作为正常对照(NC)组。收集两组一般资料及其它实验室检测指标,采用酶联免疫吸附(ELISA)法检测血清BNP及Ghrelin水平,计算胰岛素抵抗指数(HOMA-IR)、胰岛素敏感性指数(ISI)、胰岛素β细胞功能指数(HOMA-β),并分析各指标之间的关系。结果:(1)T2DM组患者血清BNP和Ghrelin水平均低于NC组,差异有统计学意义(P<0.05)。(2)Spearman秩相关分析显示:BNP和Ghrelin分别与HOMA-IR、体质指数(BMI)、空腹胰岛素(FINS)、空腹血糖(FPG)、总胆固醇(TC)呈负相关(P<0.05),与ISI、高密度脂蛋白胆固醇(HDL-C)呈正相关(P<0.05),且BNP与Ghrelin呈正相关(P<0.01)。(3)多元逐步回归分析显示:Ghrelin和FPG为影响BNP的最显著因素(β值分别为1.392和-2.282,P<0.05),常数项为23.316;BNP和FPG为影响Ghrelin的最显著因素(β值分别为0.141和-0.827,P<0.05),常数项为20.758。结论:新诊断T2DM患者血清BNP和Ghrelin均明显减低,且二者呈正相关。BNP和Ghrelin可能在2型糖尿病及IR的发生发展中存在通路,并为2型糖尿病的早期预防、诊断及治疗提供新方向。

新生大鼠胃肠道组织Ghrelin、PYY mRNA和蛋白及其下丘脑中受体mRNA的表达

目的观察新生大鼠胃肠道组织Ghrelin、酪酪肽(PYY)mRNA和蛋白以及两者位于下丘脑的受体mRNA的表达变化,并探讨其与胃肠道成熟程度的关系。方法选取0日龄和7日龄的新生大鼠各10只,分别采用Real-timePCR法和免疫组织化学法测定胃底组织GhrelinmRNA和蛋白、结肠组织PYYmRNA和蛋白、下丘脑Ghrelin和PYY受体mRNA的表达。结果 0日龄大鼠胃底Ghrelin mRNA表达高于7日龄大鼠(P<0.05),结肠PYYmRNA表达则低于7日龄大鼠(P<0.01)。0日龄大鼠胃肠道Ghrelin和PYY蛋白表达均高于7日龄大鼠(P<0.05)。0日龄与7日龄大鼠下丘脑Ghrelin和PYY受体mRNA的表达比较,差异均无统计学意义(P>0.05)。结论未成熟胃肠道组织Ghrelin和PYY蛋白合成分泌增加,起到促进胃肠道发育成熟的作用;而PYYmRNA与蛋白质表达的不平行状态提示该基因表达调控可能具有多样性。

Ghrelin在脑内的效应研究进展

脑肠肽Ghrelin(又名胃饥饿素)是生长激素促分泌激素受体的内源性配体,在外周主要由胃底细胞产生,通过刺激食欲而调节能量代谢。在脑内,Ghrelin主要在垂体和下丘脑弓状核内产生,对下丘脑内摄食、生殖、应激反应相关神经肽的合成和分泌起重要调节作用。近年来,较多的研究聚焦于Ghrelin在调节脑内学习、记忆、情绪等高级功能方面的作用,揭示了Ghrelin抗神经元凋亡,提高认知功能,调节神经内分泌轴,例如下丘脑-垂体-肾上腺轴、下丘脑-垂体-性腺轴活性而参与应激反应等显著效应。Ghrelin还极有可能在一些神经精神疾病的发病机制中扮演重要角色,因此有广阔的研究前景。文中将就相关研究进展作一综述,旨在推动对于Ghrelin在脑内的效应的研究。

Ghrelin对豚鼠胃平滑肌收缩的影响及机制

目的:探讨并比较Ghrelin及其拟似剂生长激素释放肽-6(GHRP-6)对豚鼠胃平滑肌舒缩活动的影响及机制。方法:采用电场刺激豚鼠胃底和胃窦部肌间神经方法,观察Ghrelin和GHRP-6对胃平滑肌舒缩活动的影响,并通过观察一氧化氮合酶(NOS)抑制剂Nω-硝基-L-精氨酸(L-NNA)、一氧化氮前体L-精氨酸(L-AA)对Ghrelin和GHRP-6调控胃平滑肌运动的影响以阐明其机制。结果:不同频率(1～16Hz)电刺激胃底部肌间神经,平滑肌条呈现开电刺激(on-re-sponse)的舒张波和随后出现的断电刺激(off-response)收缩波,其中产生的开电刺激舒张效应可被L-NNA消除,而断电刺激诱导的收缩效应可被阿托品和胍乙啶(NANC)阻断。在胃底部,Ghrelin和GHRP-6可使开电刺激诱导的平滑肌舒张活动减弱,断电刺激诱导的肌条收缩活动增强,且Ghrelin作用明显强于GHRP-6。L-NNA可显著增强Ghrelin和GHRP-6的促平滑肌收缩效应,但L-AA可显著减弱该作用。在胃窦部,电场刺激肌间神经,舒张波消失,仅出现断电刺激的收缩波。Ghrelin和GHRP-6均可使该收缩作用增强。结论:Ghrelin和GHRP-6均可通过肌间神经丛促进胃底部、胃窦部平滑肌收缩,该效应可能与一氧化氮通路有关。

胃旁路手术对高脂饮食诱导肥胖大鼠血浆ghrelin、GLP-1、PYY的影响

目的探讨胃旁路手术对高脂饮食诱导的肥胖大鼠血浆生长激素释放肽(ghrelin)、胰高血糖素样肽-1(GLP-1)、胃肠激素肽(PYY)的影响。方法将30只雄性Wistar大鼠随机分为正常饮食组(ND组)10只、高脂饮食组20只,分别给予正常饮食及高脂饮食喂养,喂养12周后,高脂饮食组成功建模肥胖大鼠16只,随机分为高脂饮食假手术组(HFD组)8只,高脂饮食+Roux-en-Y胃旁路手术(RYGB)组(HFD+RYGB组)8只,HFD+RYGB组大鼠行RYGB,ND组及HFD组行假手术。4周后处死全部大鼠,收集血样采用ELISA法测定血浆生长激素释放肽、胰高血糖素样肽-1、胃肠激素肽浓度。结果与ND组比较,HFD组大鼠体重增加,HFD+RYGB组大鼠体重低于HFD组,3组大鼠的摄食量比较差异无统计学意义;与ND组比较,HFD组大鼠空腹血糖与胰岛素水平升高,HFD+RYGB组大鼠空腹血糖与胰岛素水平较HFD组下降,但差异无统计学意义;HFD组大鼠血浆ghrelin、PYY浓度高于ND组,HFD+RYGB组大鼠血浆ghrelin、GLP-1浓度高于HFD组,PYY浓度低于HFD组,差异有统计学意义(P<0.05)。结论肥胖大鼠RYGB术后体重减轻,血浆GLP-1、PYY、ghrelin循环水平改变。