RouxenY胃旁路术对肥胖症大鼠空肠糖异生的影响

颜勇; 李旭忠; 周舟; 王时光; 周联明; 单远洲; 胡承; 张学利

doi:10.3760/cma.j.issn.1673-9752.2015.11.012

RouxenY胃旁路术对肥胖症大鼠空肠糖异生的影响

Effects of RouxenY gastric bypass on the jejunal gluconeogenesis in obese rats

摘要

摘要: 目的:探讨RouxenY胃旁路术(RYGB)对肥胖症大鼠空肠糖异生的影响及作用机制。
方法将高脂诱导肥胖症的40只SD大鼠按随机数字表法分为空白组(未行手术)、假手术组(与手术组对应位置切开缝合)、匹配饮食组(行假手术并保持与手术组相同进食量)和手术组(行RYGB)，每组10只。(1)定期测量大鼠体质量、进食量；(2)术前、术后2周及10周行口服葡萄糖耐量试验(OGTT)、胰岛素耐量试验(ITT)评价大鼠糖耐量及胰岛素敏感性；(3)术后10周检测各组大鼠空腹血清TC、TG、游离脂肪酸水平(FFA)；(4)留取大鼠空肠组织行病理学检查；(5)采用RTPCR和Western blot检测各组大鼠空肠黏膜组织中磷酸烯醇式丙酮酸羧激酶(PEPCK)、葡萄糖6磷酸酶α(G6Pase)mRNA和蛋白表达水平。符合正态分布的计量资料以±s表示，多组比较采用单因素方差分析，两两比较采用LSD检验。重复测量数据采用重复测量方差分析。
结果:(1)空白组、假手术组、匹配饮食组、手术组大鼠术前至术后10周体质量变化分别为(325±9)g～(451±18)g、(327±11)g～(446±14)g、(330±8)g～(442±15)g、(328±10)g～ (364±23)g。4组大鼠术前至术后10周体质量变化趋势比较，差异有统计学意义(F=422.03，P<0.05)。术后1～4周，假手术组大鼠体质量与空白组比较，差异有统计学意义(P<0.05)。假手术组与匹配饮食组大鼠术后体质量各时间点比较，仅术后6周差异有统计学意义(P<0.05)，其他时间点差异无统计学意义(P>0.05)。术后4～10周，手术组大鼠体质量分别与空白组、假手术组和匹配饮食组比较，差异均有统计学意义(P<0.05)。空白组、假手术组、手术组大鼠术前至术后10周进食量变化分别为：(25.3±1.4)g～(27.0±1.9)g、(24.9±1.3)g～(27.8±2.1)g、(25.4±1.6)g～(18.9±1.4)g，3组大鼠术前至术后10周进食量变化趋势比较，差异有统计学意义(F=64.66，P<0.05)。术后1～2周，假手术组大鼠进食量与空白组比较，差异有统计学意义(P<0.05)；而术后4～10周差异无统计学意义(P>0.05)。术后2～10周，手术组大鼠进食量分别与空白组和假手术组比较，差异均有统计学意义(P<0.05)。(2)空白组、假手术组、匹配饮食组和手术组大鼠术前至术后10周OGTT曲线下面积分别为：(1 162±58)mmol/(L·min)～(1 181±66)mmol/(L·min)、(1 168±135)mmol/(L·min)～(1 175±116)mmol/(L·min)、(1 159± 92)mmol/(L·min)～(1 117±75)mmol/(L·min)、(1 189±108)mmol/(L·min)～(940±90)mmol/ (L·min)；4组大鼠术前至术后10周ITT曲线下面积分别为：(533±80)mmol/(L·min)～(512± 95)mmol/(L·min)、(498±75)mmol/(L·min)～(545±73)mmol/(L·min)、(519±125)mmol/(L·min)～(538±92)mmol/(L·min)、(513±78)mmol/(L·min)～(426±36)mmol/(L·min)，4组大鼠术前至术后10周OGTT和ITT曲线下面积变化趋势比较，差异均有统计学意义(F=14.03，6.58，P<0.05)。(3)空白组、假手术组、匹配饮食组和手术组大鼠术后10周空腹血清TC分别为(5.41±0.19)mmol/L、(5.51± 0.16)mmol/L、(5.32±0.41)mmol/L、(4.04±0.20)mmol/L；TG分别为(6.97±0.25)mmol/L、(6.88± 0.32)mmol/L、(6.71±0.28)mmol/L、(4.05±0.29)mmol/L；FFA分别为(1.51±0.08)mmol/L、(1.53± 0.05)mmol/L、(1.44±0.11)mmol/L、(0.98±0.09)mmol/L；4组大鼠上述指标比较，差异均有统计学意义(F=67.56，234.92，83.47，P<0.05)。(4)术后大鼠空肠组织病理学检查显示：手术组大鼠空肠组织与空白组、假手术组和匹配饮食组比较，空肠增生肥大，肠壁增厚，肠绒毛增长。(5)空白组、假手术组、匹配饮食组和手术组大鼠空肠黏膜组织中PEPCK mRNA表达量分别为1.00±0.11、1.04±0.14、1.07±0.19、 1.44±0.10；G6Pase mRNA表达量分别为1.00±0.16、1.08±0.13、0.96±0.13、1.33±0.11。PEPCK蛋白相对表达量分别为105±11、96±10、99±15、129±16；G6Pase蛋白相对表达量分别为77±17、66±10、79±13、99±13；4组大鼠上述指标比较，差异均有统计学意义(F=19.80，13.52，11.85，9.29，P<0.05)。
结论RYGB可改善肥胖症大鼠的代谢症状，其作用机制可能与术后空肠糖异生增强有关。

Abstract: Objective:To investigate the effects and mechanism of RouxenY gastric bypass（RYGB）on the jejunal gluconeogenesis in obese rats.
Methods:Forty high fat dietinduced obese rats were divided into the blank group, sham surgery ad libitum fed (SA) group，sham surgery pairfed (SPF) group and RYGB group according to the random number table, with 10 rats in each group. (1) The body weight and food intake of rats were regularly measured. (2)The oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were done before operation and at postoperative week 2, 10 to evaluate glucose tolerance and insulin tolerance in rats. (3) The fasting serum TC, TG and free fatty acid were monitored at postoperative week 10. (4) Jejunal tissues of rats were abstracted for pathological examination. (5)The mRNA and protein expressions of phosphoenolpyruvate carboxykinase (PEPCK) and glucose6phosphatase (G6Pase) were detected by RTPCR and Western blot test, respectively. Measurement data were presented as ±s. Comparisons among the groups were analyzed using oneway ANOVA and pairwise comparisons were analyzed using LSD test. Repeated measures data were analyzed by the repeated measures ANOVA.
Results:(1)The body weight was changed from preoperation (325±9)g to (451±18)g at postoperative week 10 in the blank group, from (327±11)g to (446±14)g in the SA group, from (330±8)g to (442±15)g in the SPF group, from (328±10)g to (364±23)g in the RYGB group, showing significant difference in the changing trends among the 4 groups (F=422.03, P<0.05). There was significant difference between the SA group and the blank group in the body weight from postoperative week 1 to week 4 (P<0.05). There was significant difference between the SA group and the SPF group in the body weight at week 6 after surgery (P<0.05) and no significant difference at other time points (P>0.05). There was significant difference in the body weight from week 4 to week 10 after surgery between the RYGB group and the blank group, SA group and the SPF group, respectively (P<0.05). The food intake was changed from preoperative (25.3±1.4)g to (27.0±1.9)g at postoperative week 10 in the blank group, from (24.9±1.3)g to (27.8±2.1)g in the SF group, and from (25.4±1.6)g to (18.9±1.4)g in the RYGB group, showing significant differences in the changing trends among the 3 groups (F=64.66, P<0.05). There was significant difference in the food intake between the SF group and the blank group from week 1 to week 2 after surgery (P<0.05), and no significant difference from week 4 to week 10 after surgery (P>0.05). From week 2 to week 10 after surgery, there was significant difference between the RYGB group and the blank group or the SA group, respectively (P<0.05). (2)The areas under the curve of OGTT was changed from preoperation (1 162± 58)mmol/(L·minutes) to (1 181±66)mmol/(L·minutes) at postoperative week 10 in the blank group, from (1 168±135)mmol/(L·minutes) to (1 175±116)mmol/(L·minutes) in the SF group, from (1 159± 92)mmol/(L·minutes) to (1 117±75)mmol/(L·minutes) in the SPF group, and from (1 189±108)mmol/(L·minutes) to (940±90)mmol/(L·minutes) in the RYGB group. The areas under the curve of ITT was changed from preoperative (533±80)mmol/(L·minutes) to (512±95)mmol/(L·minutes) at postoperative week 10 in the blank group, from (498±75)mmol/(L·minutes) to (545±73)mmol/(L·minutes) in the SF group, from (519±125)mmol/(L·minutes) to (538±92)mmol/(L·minutes) in the SPF group, and from (513±78)mmol/(L·minutes) to (426±36)mmol/(L·minutes) in the RYGB group. There were significant differences in the areas under the curve of OGTT and ITT among the 4 groups (F=14.03, 6.58, P<0.05). (3)The fasting serum TC, TG and FFA level were (5.41±0.19)mmol/L, (6.97±0.25)mmol/L, (1.51± 0.08)mmol/L in the blank group, (5.51±0.16)mmol/L, (6.88±0.32)mmol/L，(1.53±0.05)mmol/L in the SA group, (5.32±0.41)mmol/L, (6.71±0.28)mmol/L, (1.44±0.11)mmol/L in the SPF group, (4.04±0.20)mmol/L, (4.05±0.29)mmol/L, (0.98±0.09)mmol/L in the RYGB group, with significant differences among the 4 groups (F=67.56, 234.92, 83.47, P<0.05). (4)The postoperative pathological examinations showed hypertrophy, bowel wall thickening, villus increasing of jejunum tissues of rats in the RYGB group compared with the blank group, the SA group, and the SPF group. (5)The jejunum mucosa mRNA and protein expressions of PEPCK and G6Pase were 1.00±0.11, 1.00±0.16, 105±11, 77±17 in the blank group, 1.04±0.14, 1.08±0.13, 96±10, 66±10 in the SA group, 1.07±0.19, 0.96±0.13, 99±15, 79±13 in the SPF group, and 1.44±0.10, 1.33±0.11, 129±16, 99±13 in the RYGB group, with significant differences among the 4 groups (F=19.80, 13.52, 11.85, 9.29, P<0.05).
Conclusion:RYGB can improve the metabolic conditions of obese rats, the mechanism of which may be related with increased jejunal gluconeogenesis.

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