改良胃袖状切除对肥胖大鼠ghrelin及胰高血糖素样肽-1水平的影响

目的根据胃肠道不同部位激素分泌的特点,探讨一种新的长期减重效果明显的手术方式。方法高脂饮食诱导Wistar肥胖大鼠35只,然后将诱导成功的肥胖大鼠按完全随机方法分为改良胃袖状切除术组(n=12)、胃袖状切除术组(n=12)及假手术组(n=11)3组,分别比较3组大鼠术前、术后连续8周的体重和摄食量,以及术前及术后第8周时外周血清中生长激素释放肽ghrelin和胰高血糖素样肽-1(GLP-1)水平的变化。结果①大鼠体重和摄食量:3组间术前大鼠的体重和摄食量差异均无统计学意义(P>0.05)。改良胃袖状切除术组和胃袖状切除术组术后1～8周,大鼠的体重均较假手术组明显下降(P<0.05),改良胃袖状切除术组较胃袖状切除术组大鼠的体重也明显下降(P<0.05)。改良胃袖状切除术组术后1～8周大鼠的摄食量较假手术组明显减少(P<0.05),改良胃袖状切除术组于术后3、6、7及8周大鼠的摄食量较胃袖状切除术组大鼠明显减少(P<0.05)。②外周血清中ghrelin和GLP-1水平:3组间术前大鼠ghrelin和GLP-1水平变化差异均无统计学意义(P>0.05);术后第8周,血清ghrelin水平改良胃袖状切除术组和胃袖状切除术组均较假手术组明显下降(P<0.05),改良胃袖状切除术组又较胃袖状切除术组明显下降(P<0.05);GLP-1水平改良胃袖状切除术组较假手术组和胃袖状切除术组明显升高(P<0.05)。同时,术后第8周时改良胃袖状切除术组和胃袖状切除术组ghrelin水平较术前明显下降(P<0.05),GLP-1水平在改良胃袖状切除术组较术前明显升高(P<0.05)。结论改良胃袖状切除术在肥胖大鼠模型中成功实施为进一步探索其临床应用提供了可能。     

胃转流术对2型糖尿病大鼠的血糖及胰高血糖素样肽-1的影响

目的 观察胃转流术(GBP)对糖尿病大鼠血糖的控制效果及胰高血糖素样肽-1(GLP-1)的影响.方法 采用链脲佐菌素建立糖尿病SD大鼠模型20只,随机分为糖尿病手术组(DO组)和糖尿病对照组(DC组),另取20只非糖尿病大鼠随机分为正常对照组(NC组)和正常手术组(NO组).分别检测各组大鼠术前、术后72 h、1周、4周和8周空腹血糖水平以及血清GLP-1浓度.结果 术前DO组与DC组以及NC组与NO组大鼠空腹血糖之间的比较差异均无统计学意义(P＞0.05);DO组大鼠术后空腹血糖进行性下降,术后8周由术前的(20.84±1.98) mmol/L下降到(5.56±0.11) mmol/L(P＜0.05);DC组大鼠术前及术后各时相的差异无统计学意义(P＞0.05).DO组和NO组大鼠术后血清GLP-1浓度出现明显升高(P＜0.05),术后8周分别由术前的(7.10±0.55)、(10.73 ±0.67) pmol/L上升到(26.48±1.14)、(13.98±0.92) pmol/L(P＜0.05).结论 GBP对2型糖尿病大鼠具有明显的降糖作用,GLP-1的升高在其中起着重要作用,但对正常大鼠血糖无影响.     

胃袖状切除附加空回肠吻合术对ZDF大鼠GLP-1蛋白表达的影响

目的:探讨胃袖状切除加空回肠侧侧吻合术(sleeve gastrectomy plus side-to-side jejunoileal anastomosis,JI-SG)对糖尿病肥胖(Zucker diabetic fatty,ZDF)大鼠末端回肠黏膜组织胰高血糖素样肽-1(glucagon-like peptide 1,GLP-1)蛋白表达及空腹血糖的影响,探讨其降糖的可能机制。方法:将30只ZDF大鼠随机分为假手术(sham surgery,SS)组、胃袖状切除(sleeve gastrectomy,SG)组、JI-SG组,术后同等条件下饲养12周,观察血清血糖、GLP-1及胰岛素水平,于术后12周末检测GLP-1蛋白在回肠末端组织中的表达。结果:JI-SG组、SG组回肠末端GLP-1蛋白表达阳性率高于SS组(P<0.05),伴有L细胞增生;JISG组较SG组有显著性升高(P<0.05)。SG组、JI-SG组血糖水平较SS组明显下降(P<0.05),同时JI-SG组较SG组降糖效果更加明显(P<0.05)。SG组、JI-SG组血清胰岛素水平较SS组明显下降(P<0.05),同时JI-SG组低于SG组(P<0.05)。SG组、JI-SG组血清GLP-1水平较SS组明显升高(P<0.05),同时JI-SG组高于SG组(P<0.05)。结论:JI-SG可显著增强回肠末端GLP-1蛋白表达,同时伴有L细胞增生,可能是其具有显著且持续稳定降糖作用的原因。     

胰高血糖素样肽-2对烧伤大鼠肠粘膜细胞增殖的影响

目的　探讨胰高血糖素样肽 2 (GLP 2 )对烧伤大鼠肠粘膜细胞增殖及肠粘膜结构的影响。　方法　 5 5只Wistar大鼠随机分为烧伤组、GLP 2组 (烧伤后经GLP 2处理 ,2 0 0 μg/kg ,2次 /d腹腔注射 )与正常对照组。前两组动物于 30 %TBSAⅢ度烧伤后 6、12h及 1、3、5d分别处死 ,另处死正常对照组大鼠。检测各组增殖细胞核抗原 (PCNA)、细胞周期蛋白CyclinD的表达情况以及血浆二胺氧化酶 (DAO)的活性 ,并行肠粘膜组织学观察。　结果　与正常对照组比较 ,烧伤组伤后 6、12hPCNA表达稍有增强 ,伤后 1d减弱 ,3d时最低 ,5d时仍低于正常 ;GLP 2组PCNA表达的变化在伤后早期与烧伤组基本一致 ,但伤后 3、5d时强于烧伤组。烧伤组大鼠肠粘膜CyclinD蛋白在伤后 6、12h略有升高 ,但 1d时迅速下降至伤前的 4 0 % ,而GLP 2组CyclinD蛋白表达在伤后 1、3、5d高于烧伤组。大鼠烧伤后血浆DAO活性明显升高 ,经GLP 2治疗 5d后该指标明显降低 (P <0 .0 1)。组织学观察见GLP 2组肠绒毛排列较为规则 ,长短较一致 ,未见明显的上皮脱落。　结论　大鼠烧伤后腹腔给予外源性GLP 2能减轻肠粘膜损伤 ,其机制可能与GLP 2使PCNA、ClyclinD表达增加、促进受损肠粘膜细胞增殖有关。     

胰高血糖素样肽-2对短肠大鼠残留小肠代偿的影响

目的研究胰高血糖素样肽-2(GLP-2)对短肠大鼠残留小肠形态及功能代偿的影响。方法将20只切除小肠75%的大鼠随机分成对照组和GLP-2组,术后1-5 d内自由进食。GLP-2组每日2次腹腔注射GLP-2(250μg·kg~(-1)·d~(-1))；对照组每日2次腹部皮下注射生理盐水0．5 ml；另设1组正常进食大鼠作空白对照。术后第6天行残留小肠黏膜形态学检测、细胞增殖核心抗原(PCNA)测定,钠葡萄糖共同转运体(SGLT1)和二肽转运体(PEPT1)的mRNA表达检测以及在体小肠循环灌流实验测定大鼠回肠的单位长度及单位重量的葡萄糖吸收率。结果GLP-2组残留小肠黏膜形态学指标、PCNA指数显著高于对照组；而小肠黏膜细胞凋亡显著低于对照组；残留回肠SGLT1和PEPT1的mRNA表达显著高于对照组；均P＜0．05。但两组灌洗段回肠每g湿重葡萄糖吸收率差异无统计学意义(P＞0．05)。结论GLP-2能刺激小肠黏膜上皮增生、抑制凋亡,促进短肠大鼠残留小肠黏膜的形态及功能代偿。     

胃肠道营养物质代谢与胰高血糖素样肽-1水平改变

目的介绍胃肠道营养物质代谢与胰高血糖素样态-1(GLP-1)水平关系的研究现状。方法收集近年来国内、外有关胃肠道营养物质代谢与GLP-1水平关系的文献并作综述。结果 GLP-1影响胰岛素的分泌及其敏感性,在糖代谢恢复中发挥主导作用。胃肠道营养物质代谢影响GLP-1水平。胃转流术(GBP)治疗2型糖尿病(T2DM)可能主要与其影响GLP-1水平有关。结论胃肠道营养物质代谢调控GLP-1水平在GBP治疗T2DM中起了重要作用,相应的深入研究将为T2DM的治疗开辟一个新的领域。     

胰高血糖素样肽-1及其类似物保护认知功能的研究进展

背景 认知功能障碍是指学习记忆、思维判断等大脑高级功能异常,目前尚无确切的防治药物.2型糖尿病被公认为发生认知功能障碍的危险因素.胰高血糖素样肽-1（glucagon-like peptide-1,GLP-1）及其类似物是一种针对2型糖尿病的新型降糖药,研究发现其还具有保护认知功能的作用. 目的 为GLP-1及其类似物应用于临床防治认知功能障碍提供理论依据. 内容 就GLP-1及其类似物的保护认知功能的研究现状作一综述. 趋向 有望成为防治认知功能障碍等神经病理性疾病的新型药物.     

胃袖状切除术加空肠-回肠旁路术对肥胖合并糖尿病大鼠体重和代谢调节作用研究

目的 研究胃袖状切除术（SG）加空肠-回肠旁路术（JIB）对大鼠体重及糖代谢的影响及其机制。方法 于2018年9-11月在复旦大学附属浦东医院完成研究。将12只肥胖合并2型糖尿病（ZDF,fa/fa）大鼠随机等分为两组,分别行SG+JIB（SG+JIB组）和SG+假手术（SG+Sham组）。另有5只ZDF（fa/+）大鼠作为正常对照组。检测术前及术后2、4周大鼠的体重、空腹血糖、摄食量、口服糖耐量试验（OGTT）以及血浆胰高血糖素样肽-1（GLP-1）水平的变化。结果 SG+JIB组与SG+Sham组大鼠术前基线差异无统计学意义（P>0.05）。与SG+Sham组相比,SG+JIB组术后2周（17.3 mmol/L vs. 8.7 mmol/L）、4周（21.4 mmol/L vs. 11.9 mmol/L）空腹血糖均显著降低（P<0.0001）,口服糖耐量也明显改善,两组血糖曲线下面积（180 min总和）在术后2周分别为4221和2964（P<0.0001）,术后4周分别为4104和3388（P<0.01）。同时,术后4周时SG+JIB组GLP-1水平显著高于SG+Sham组（64.6 pmol/L vs. 30.5 pmol/L,P<0.001）。SG+JIB组大鼠每日摄食量和体重仅在术后2周较SG+Sham组减少,术后4周两组差异无统计学意义（P>0.05）。结论 SG+JIB手术可进一步增强SG手术的代谢调节作用,然而对于体重并无显著的额外减轻,建议将SG+JIB手术推荐给需要进一步增强代谢调节的病人,而不建议推荐给以额外降低体重为目的的病人。     

不同剂量胰升血糖素样肽-1对大鼠肝切除术后糖代谢的影响

目的:探讨不同剂量胰升血糖素样肽-1（GLP-1）对大鼠肝切除手术后早期糖代谢紊乱的影响。方法:方法通过大鼠肝切除术观察手术后1 d葡萄糖耐量的改变与GLP-1，胰岛素(I)和胰升血糖素(G)的关系，以及静脉输注不同剂量GLP-1的影响。结果:大鼠肝切除术后第1天静脉葡萄糖耐量实验的峰值血糖及30 min血糖均明显高于正常对照组（ 均P<0.01），且曲线下面积（AUC 0-30）也明显高于正常对照组(P<0.01)；GLP-1低剂量组术后1 d峰值血糖与肝切除手术组间的差异无显著性（P>0.05）；GLP-1高剂量组术后1 d峰值血糖明显低于肝切除手术组和GLP-1低剂量组(P<0.05和P< 0.01)， 30 min血糖明显低于肝切除手术组(P<0.01), AUC 0-30明显低于肝切除手术组和GLP-1低剂量组(均为P<0.01)。肝切除手术组术后1 d胰岛素明显下降，胰升血糖素明显升高（P<0.05），致I/G值下降。GLP-1低剂量组术后1 d胰岛素明显低于高剂量组（P<0.05），胰升血糖素则明显升高（P<0.05），致I/G值明显低于高剂量组（P<0.01）。结论:大鼠肝切除术后早期，GLP-1的促进胰岛素分泌和抑制胰升血糖素释放的作用减弱，增加剂量后仍可增强其效应，进一步改善机体对葡萄糖的利用。     

胰高血糖素样肽-2对短肠大鼠残留小肠代偿的影响

目的　研究胰高血糖素样肽 2 (GLP 2 )对短肠大鼠残留小肠代偿的影响及机制。方法　 75 %小肠切除大鼠随机分成空白 (SB)组、生长激素 (GH )组和GLP 2组。术后 6d行残留回肠黏膜形态学检测、细胞增殖核心抗原 (PCNA)测定及原位末端标记 (INST法 )染色。结果　GLP 2组回肠黏膜形态学指标显著高于SB组 (P <0 .0 5 ) ,并且其黏膜厚度显著高于GH组 (P <0 .0 5 )。GLP 2组PCNA指数显著高于SB组 (0 .5 1± 0 .0 9与 0 .40± 0 .0 6比较 ,P <0 .0 5 ) ,但和GH组比较差异无统计学意义 (P >0 .0 5 )。GLP 2组细胞凋亡显著低于SB组 (67.7± 10 .1与 81.7± 12 .9比较 ,P <0 .0 5 ) ,但和GH组比较差异无统计学意义 (P >0 .0 5 )。结论　GLP 2能刺激小肠黏膜上皮增生 ,抑制凋亡 ,显著促进短肠大鼠残留小肠黏膜的形态代偿。     

Sleeve Gastrectomy and Gastric Banding: Effects on Plasma Ghrelin Levels

Background: Different changes of plasma ghrelin levels have been reported following gastric banding, Roux-en-Y gastric bypass, and biliopancreatic diversion. Methods: This prospective study compares plasma ghrelin levels and weight loss following laparoscopic sleeve gastrectomy (LSG) and laparoscopic adjustable gastric banding (LAGB) in 20 patients. Results: Patients who underwent LSG (n=10) showed a significant decrease of plasma ghrelin at day 1 compared to preoperative values (35.8 ± 12.3 fmol/ml vs 109.6 ± 32.6 fmol/ml, P=0.005). Plasma ghrelin remained low and stable at 1 and 6 months postoperatively. In contrast, no change of plasma ghrelin at day 1 (71.8 ± 35.3 fmol/ml vs 73.7 ± 24.8 fmol/ml, P=0.441) was found in patients after LAGB (n=10). Increased plasma ghrelin levels compared with the preoperative levels at 1 (101.9 ± 30.3 fmol/ml vs 73.7 ± 24.8 fmol/ml, P=0.028) and 6 months (104.9 ± 51.1 fmol/ml vs 73.7 ± 24.8 fmol/ml, P=0.012) after surgery were observed. Mean excess weight loss was higher in the LSG group at 1 (30 ± 13% vs 17 ± 7%, P=0.005) and 6 months (61 ± 16% vs 29 ± 11%, P=0.001) compared with the LAGB group. Conclusions: As a consequence of resection of the gastric fundus, the predominant area of human ghrelin production, ghrelin is significantly reduced after LSG but not after LAGB. This reduction remains stable at follow-up 6 months postoperatively, which may contribute to the superior weight loss when compared with LAGB.     

Sleeve Gastrectomy Improves Glucose Homeostasis in Zucker Diabetic Fatty Rats

Background

Bariatric surgery improves glucose homeostasis, but the mechanism of action is poorly understood. The aim of this study was to assess the effect of sleeve gastrectomy (SG) on glucose homeostasis in two obese populations of rats.

Methods

Two strains of rats [Zucker fatty (ZF) and Zucker diabetic fatty (ZDF)] were each divided into two groups: sham and SG. Food intake was measured daily, and weight was measured bi-weekly. Oral glucose tolerance testing (OGTT) was performed before and 45?days after surgery.

Results

In both strains of rats, there was no statistical difference in food intake and weight gain between the sham and SG rodents before and after surgery. In ZF rats, there was no change in fasting glucose or OGTT area under the curve (AUC) before or 45?days after surgery. In the ZDF rodents, the mean preoperative fasting glucose and OGTT AUC was 204?±?25 and 25,441?±?2,648, respectively. At 45?days after surgery, mean fasting glucose significantly increased in the sham (sham?=?529?±?26, p?=?0.0003) but not in the SG rodents (SG?=?289?±?46, p?=?0.1113). In ZDF sham animals, OGTT at 45?days showed a higher AUC compared to before surgery (44,983?±?6,338, p?=?0.006), whereas in ZDF SG rodents, the increase in AUC glucose approached but did not reach statistical significance (35,553?±?3,925, p?=?0.06).

Conclusions

In ZF and ZDF rodents, SG did not influence food intake and weight evolution. In ZDF rodents, diabetes progressed in the sham group but not in the SG group.     

胃袖带切除术对GK大鼠2型糖尿病的影响及其机理

目的研究胃袖带切除术（sleevegastrectomy,SG）对GK大鼠2型糖尿病（type2diabetesmellitus,T2DM）的治疗作用及其可能机理。方法将13只12周龄的GK大鼠随机分为2组：SG组7只和假手术组（SO组）6只,分别行SG术和假手术。于术前及术后1、4、10和26周测量2组大鼠的体质量、24h进食量、空腹血糖值、血清胰高血糖素样肽-1（glucagon-likepeptide-1,GLP-1）和血清生长激素释放肽（Ghrelin）浓度;于术后10周检测2组大鼠的粪便能量含量,并进行口服葡萄糖耐量实验（OGTT）和胰岛素耐受性实验（ITT）。结果①体质量：各时点2组大鼠的体质量比较差异均无统计学意义（P〉0．05）;与术前比较,术后1周2组大鼠的体质量均降低（P〈0．01）,术后10和26周的体质量均增加（P〈0．01）。②24h进食量：与SO组比较,术后4和10周SG组大鼠的24h进食量均较低（P〈0。05）。与术前比较,SG组大鼠术后1、4及10周的进食量均较低（P〈0．05）,SO组大鼠术后1周的进食量低于术前（P〈0．05）。③空腹血糖值：与SO组比较,术后各时点SG组大鼠的空腹血糖值均较低（P〈0．01）。与术前比较,SG组大鼠术后各时点的空腹血糖值均较低（P〈0．01）,而SO组大鼠仅术后1周明显低于术前∽〈0．OD。④血清GLP-1水平：与SO组比较,术后4、10及26周SG组大鼠的血清GLP．1水平均较高（P〈0．05）。与术前比较,术后4、10及26周SG组大鼠的血清GLP-1水平较高（P〈0．05）,而术后SO组大鼠的血清GLP．1水平无明显变化（P〉0．05）。⑤血清Ghrelin水平：与SO组比较,术后各时点SG组大鼠的血清Ghrelin水平均较低（P〈0．01）。与术前比较,术后各时点SG组大鼠的血清Ghrelin水平均较低（P〈0．001）,而SO组大鼠的血清Ghrelin水平无明显变化（P〉0．05）。⑥曲线下面积（AUC）：SG组大鼠的AUC（OGTT和ITT）均较SO组低（P〈0．01）。结论SG术可以明显降低GK大鼠的空腹血糖值,改善葡萄糖耐量及增强胰岛素敏感性,该作用可能是GLP．1、Grelin等多种胃肠道激素共同作用的结果。SG术可能是潜在的非肥胖型T2DM的治疗方法。     

The Impact of Laparoscopic Sleeve Gastrectomy on Plasma Ghrelin Levels: a Systematic Review

Within the last decade, several authors have proposed laparoscopic sleeve gastrectomy (LSG) as a potential definitive treatment for morbid obesity. While initially perceived as being a solely restrictive procedure, it is now theorized to have additional hormonal effects (primarily the reduction of circulating levels of plasma ghrelin). However, there is limited supporting evidence for this claim. Therefore, the purpose of our study is to conduct a systematic review of the literature to clarify the effects of LSG on modulation of postoperative ghrelin concentrations. A comprehensive literature search for published or unpublished studies of sleeve gastrectomy (SG) and ghrelin written in English prior to February 2013 was performed using Pubmed, EMBASE, the Cochrane database, and Scopus. Gray literature was also searched through Google. Inclusion criteria for searches were: randomized controlled trials, non-randomized clinical trials, retrospective and prospective cohort studies, or case series. Seven studies were deemed suitable for analysis. The mean patient age was 43?±?8.8 years and female percentage was 74.4?±?15.3 %. The mean initial BMI was 46.2?±?7.8 and mean follow-up time was 9.5?±?15 months. The mean postoperative BMI was 37.3?±?5.8 over the same follow-up period. Pooled mean preoperative ghrelin levels were 698.4?±?312.4 pg/ml and postoperative levels were 414.1?±?226.3 pg/ml (P?<?0.0001). Pooled analysis of ghrelin levels at 3, 6, and 12 months showed a significant reduction in circulating levels. Our systematic review shows that LSG has a significant effect on ghrelin levels, leading to considerable reduction in circulation levels following surgery. Further research and standardization is necessary to clearly establish a causative relationship between LSG and reduction of circulating ghrelin levels.     

Long-Term Plasma Ghrelin and Leptin Modulation After Sleeve Gastrectomy in Wistar Rats in Comparison with Gastric Tissue Ghrelin Expression

Background  

Sleeve gastrectomy (SG) is a gaining ground operation amongst the ones applied for treatment of morbid obesity. Though SG is a food limiting operation, the removal of the gastric fundus where ghrelin is mainly produced may indicate a hormonal impact of the procedure. The purpose of this experiment is to study how SG affects the levels of ghrelin and leptin.     

Plasma Ghrelin Modulation in Gastric Band Operation and Sleeve Gastrectomy

BACKGROUND: Gastric band operation and sleeve gastrectomy are increasingly popular bariatric surgeries for weight loss. The purpose of this study is to investigate the changes in plasma ghrelin levels and hypothalamic ghrelin receptor expression with weight loss achieved through these surgeries. METHODS: Twenty-four high fat diet-induced obese rats were used to investigate the effects of gastric band and sleeve operation on Body Mass Index, fat mass, plasma ghrelin levels, and hypothalamic growth hormone secretagogue receptor 1a (GHS-R 1a) protein expression in hypothalamus. In comparison, data of patients who received laparoscopic adjustable gastric banding (LAGB) and laparoscopic sleeve gastrectomy (LSG) in our hospital in 2005 were also summarized. RESULTS: Body weights and fat mass decreased significantly in rats that received operation. Plasma ghrelin concentrations in the sleeve group were 0.4-fold of control rats and about 2-fold of control in the gastric band group. GHS-R1a protein expression in hypothalamus was 1.5-fold in the sleeve group compared with control group, while it was only 0.9-fold in the gastric band group. Clinical data showed that patients in the LSG group lost 60% excess body weights in 2 years follow-up. After operation, fasting plasma ghrelin concentrations in LAGB was significantly higher than the LSG group. CONCLUSION: Both LAGB and LSG can decrease patients' excess body weights and fat mass. Plasma ghrelin levels are down-regulated with LSG operation but up-regulated with LAGB operation. Hypothalamic GHS-R1a expression is elevated in sleeve gastrectomy.     

Effects of Sleeve Gastrectomy and Medical Treatment for Obesity on Glucagon-like Peptide 1 Levels and Glucose Homeostasis in Non-diabetic Subjects

Background  

The effects of medical and surgical treatments for obesity on glucose metabolism and glucagon-like peptide 1 (GLP-1) levels independent of weight loss remain unclear. This study aims to assess plasma glucose levels, insulin sensitivity and secretion, and GLP-1 levels before and after sleeve gastrectomy (SG) or medical treatment (MED) for obesity.