胃袖状切除对GK大鼠血糖、ghrelin和胰高血糖素样肽-1水平的影响

目的探讨胃袖状切除术的降糖作用及其作用机理。方法按照随机数字表达法将非肥胖的2型糖尿病大鼠(GK大鼠)分为袖状胃切除组(SG组)、假手术组(SO组)、饮食配对组(PF组)和空白对照组(BC组)。动态观察术前和术后24周内各组大鼠体重、空腹血糖、葡萄糖耐量(口服葡萄糖耐量试验,OGTT)、胰岛素耐量(胰岛素耐量试验,ITT)及胰岛素、生长激素释放肽ghrelin和胰高血糖素样肽-1(GLP-1)水平的变化。结果自术后4周起SG组和PF组的体重增量开始明显小于SO组(P<0.01)。自术后2周起SG组的空腹血糖水平较其他3组明显降低(P<0.05)。自术后2周起SG组对葡萄糖的耐量较术前和其他3组相应时相明显改善(P<0.01)。术后第6周SG组对胰岛素的敏感性较SO组明显改善(P<0.05,P<0.01)。术后2~24周SG组与SO组比较,胰岛素水平的差异均无统计学意义(P>0.05),ghrelin水平明显下降(P<0.01),GLP-1水平明显升高(P<0.01)。结论胃袖状切除术的降糖效果确切,能够独立于体重的变化而直接有效地降低血糖;术后ghrelin水平下降及GLP-1水平升高可能是胃袖状切除降糖的主要机理。     

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。     

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.     

胰高血糖素样肽-1在骨质疏松症中的影响及作用机制的研究进展

胰高血糖素样肽-1受体激动剂(glucagon like peptide-1 receptor agonists, GLP-1RAs)作为一种抗糖尿病药物,近年来对骨质疏松症的影响越来越受到人们的关注。而胰高血糖素样肽-1(glucagon like peptide-1, GLP-1)在骨质疏松症患者中的具体作用及相关机制有待进一步探讨和阐明。本文回顾及总结了近年来的文献,综述了GLP-1在治疗骨质疏松症中的研究进展,希望可以为治疗骨质疏松提供新思路。     

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。     

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.     

胃袖状切除附加改良空回肠旁路术治疗病态性肥胖症(附1例报道)

目的 探讨胃袖状切除附加改良空回肠旁路术的减肥效果及其在临床中的应用价值.方法 分析我院1例行胃袖状切除附加改良空回肠旁路术治疗的病态性肥胖患者的临床资料.结果 术后随访12个月,多余体重减少达70.8%,无胃肠功能紊乱、营养障碍等并发症.结论 胃袖状切除附加改良空回肠旁路术治疗病态性肥胖近期减重效果确切、安全.     

袖状胃切除术对高脂饮食诱导的肥胖大鼠主动脉内皮细胞LOX-1表达水平的影响

目的探讨袖状胃切除术对于高脂饮食所诱导的营养性肥胖大鼠主动脉脂肪浸润及LOX-1表达的影响。方法 24只Wistar大鼠被随机分为正常喂养组(CO组)、高脂饮食组(HD组)及高脂饮食加袖状胃切除术组(SG组),其中术前CO组、HD及SG组均接受正常饮食。术后CO组接受正常饮食,HD组及SG组接受高脂饮食,分别于术后10、20及30 d检测大鼠体重变化。30 d时处死实验动物并应用ELISA法测定血浆高密度脂蛋白(HDL)和低密度脂蛋白(LDL)水平,Western blot法检查LOX-1水平,Real-time RT-PCR法检查LOX-1 mRNA表达,采用免疫组织化学方法经尼罗红染色检测主动脉内皮脂肪细胞浸润。结果 HD组大鼠术后体重明显高于另外两组(P<0.05)。CO组、HD组及SG组血浆HDL水平分别为(32.9±2.2)mg/dl(、43.4±1.4)mg/dl及(40.5±1.3)mg/dl,HD组明显高于CO组(P<0.05),HD与SG组差异无统计学意义。CO组、HD组及SG组血浆LDL水平分别为(31.8±1.6)mg/dl、(53.3±1.8)mg/dl及(37.5±1.5)mg/dl,HD组明显高于其他2组(P<0.01)。HD组的LOX-1蛋白和LOX-1 mRNA表达情况也明显高于另外两组(P<0.01)。HD组主动脉脂肪染色情况也提示HD组强于另外两组。结论高脂饮食可导致主动脉LOX-1蛋白和mRNA表达上升,袖状胃切除术后可使血浆LDL水平下降,从而使LOX-1蛋白和mRNA表达下调。     

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.     

胃促生长素对胃大部切除大鼠术后早期恢复的影响

目的探讨应用外源性胃促生长素(ghrelin)对胃大部切除术后大鼠早期恢复的影响。方法将12只胃大部切除(毕Ⅰ式)大鼠随机均分为2组,分别于腹腔内注射生理盐水或胃促生长素,称量术前和术后1~7 d的大鼠体重和每日摄食量;术后第7天处死大鼠,实时荧光定量PCR法测定大鼠胃底组织中胃促生长素mRNA表达相对量,并检测吻合口爆破压和吻合口组织中羟脯氨酸含量。结果 2组大鼠之间术前及术后1~7 d体重的差异均无统计学意义(P>0.05)。生理盐水组大鼠体重术后逐渐降低,并均明显低于术前(P<0.01),且在术后第5天达到最低(P<0.01),后逐渐增加,但仍均低于术前(P<0.01);胃促生长素组大鼠体重术后逐渐降低,除术后1 d与术前比较的差异无统计学意义(P=0.693)外,均明显低于术前(P<0.01),在术后第4天达到最低(P<0.01),后逐渐增加,但仍均低于术前(P<0.05或P<0.01)。胃促生长素组大鼠的累积摄食量为(52.50±6.77)g,明显高于生理盐水组大鼠的(45.67±7.47)g,P<0.05。术后第7天胃促生长素组大鼠胃底组织中胃促生长素mRNA表达相对量为0.08±0.04,明显低于生理盐水组大鼠的0.22±0.07(P<0.01)。胃促生长素组大鼠吻合口爆破压为(172.33±10.44)mm Hg(1 mm Hg=0.133 kPa),明显高于生理盐水组的(155.83±6.62)mm Hg,P<0.05。胃促生长素组大鼠吻合口组织中羟脯氨酸含量为(0.50±0.29)μg/mg wet tissue,明显高于生理盐水组大鼠的(0.43±0.05)μg/mg wet tissue,P<0.01。结论 胃促生长素能有效促进胃大部切除术后大鼠的早期恢复,而外源性胃促生长素的摄入可抑制机体术后早期的负反馈性代偿作用。     

Carbohydrate Content of Post-operative Diet Influences the Effect of Vertical Sleeve Gastrectomy on Body Weight Reduction in Obese Rats

Background

Vertical sleeve gastrectomy (VSG) effectively reduces body weight (BW) in obese rats and humans. However, post-surgical weight regain is frequently observed in subjects after VSG, but the underlying reasons remain poorly understood. We therefore investigated if post-surgical consumption of different diets can affect the outcome of VSG.

Methods

VSG or sham operation was performed in Long–Evans rats with diet-induced obesity (n?=?37). After post-surgical recovery, rats were fed ad libitum either with standard chow (CH), high-fat (HF) or low-carbohydrate, high-fat (LCHF) diets. BW and food intake were measured every second day; serum leptin, cholesterol, HDL cholesterol, and triglycerides were analyzed 4 weeks after surgery. Energy expenditure and locomotor activity were determined by a combined indirect calorimetry system, lean and fat mass by nuclear magnetic resonance.

Results

After 4 weeks, BW gain, fat mass, and leptin were lower in VSG rats when compared to sham controls (p?Conclusion In conclusion, consumption of a HF diet but not the more energy-dense LCHF diet reduced the effectiveness of VSG in rats.     

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.     

Eating Behavior and Glucagon-Like Peptide-1-Producing Cells in Interposed Ileum and Pancreatic Islets in Rats Subjected to Ileal Interposition Associated with Sleeve Gastrectomy

Background

Ileal interposition–sleeve gastrectomy (II–SG) has been developed as a metabolic surgery based on the hindgut hypothesis. The aim of the present study was to test this hypothesis by studying the eating behavior, metabolic changes, and glucagon-like peptide-1 (GLP-1)-producing cells in rat models.

Methods

Male Sprague–Dawley rats were subjected to laparotomy, II, SG, or II–SG. Eating behavior and metabolic parameters were monitored by an open-circuit indirect calorimeter designed for a comprehensive laboratory animal monitoring system. GLP-1-producing cells were examined by quantitative immunohistochemistry.

Results

After II alone, satiety ratio, i.e., intermeal interval/meal size, was reduced, while calorie intake was increased at 2 and 6 weeks postoperatively. Respiratory exchange ratio, VCO₂/VO₂, was increased to above 1.0 (i.e., carbohydrate metabolism) during both daytime and nighttime at 2 weeks postoperatively. After SG alone, GLP-1-producing cells were increased in the pancreatic islets (in terms of volume density), but not in the ileum (number/mm). After II–SG, the rate of eating was reduced, while meal duration (min) was increased during both daytime and nighttime at 2 weeks postoperatively. GLP-1-producing cells were increased by about 2.5-fold in the interposed ileum and also increased to the same extent in the pancreatic islets as seen after SG alone. The increased GLP-1-producing cells in the pancreatic islets after SG or II–SG were located around the insulin-producing β cells.

Conclusions

The present study provides evidence supporting the hindgut hypothesis. II–SG increased GLP-1 production both in the interposed ileum and in the pancreatic islets, leading to metabolic beneficial effects and altered eating behavior.