摘要
目的:探究大枣对2型糖尿病(T2DM)大鼠摄食及肠道炎症损伤的影响作用及机制.方法:SD大鼠随机分为空白组、T2DM模型组、大枣低剂量组(1.575 g/kg)、大枣高剂量组(9.45 g/kg),除空白组外,其余各组大鼠以高脂高糖饲料+链脲佐菌素(STZ)诱导T2DM模型,成模后给药组每日灌胃不同浓度的大枣溶液,连续4周.观察、记录大鼠的一般情况及摄食量、血糖等;检测大鼠血清中炎症因子白细胞介素1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、胰高血糖素样肽-1(GLP-1)、酪酪肽(PYY)水平,同时观察大鼠回肠病理切片组织损伤情况及细胞凋亡情况,并检测大鼠肠道中炎症与凋亡相关基因核因子-κB p65(NF-κBp65)、含半胱氦酸的天冬氦酸蛋白水解酶-3(Caspase3)的表达,以及炎症与凋亡相关蛋白Toll样受体4(TLR4)、NF-κB p65、磷酸化NF-κB p65(p-NF-κB p65)、BCL2 相关 X 蛋白(Bax)、B 淋巴细胞瘤-2(Bcl-2)、Pro Caspase3 及 Cleaved Caspase3的水平.结果:与模型组相比,给药组大鼠摄食量极显著降低(P＜0.01),血清中TNF-α、IL-1β水平均极显著降低(P＜0.01),GLP-1水平极显著升高(P＜0.01),其中PYY水平在大枣高剂量组极显著升高(P＜0.01);回肠组织炎症损伤有所改善,大枣高剂量组回肠组织细胞凋亡率极显著降低(P＜0.01);给药组肠道NF-κBp65、Caspase3 mRNA和NF-KBp65、Cleaved Caspase3蛋白表达水平均显著下调(P＜0.01,P＜0.05),大枣高剂量组p-NF-κBp65、Pro Caspase3和Bax/Bcl-2蛋白表达显著下调(P＜0.05,P＜0.01).结论:大枣能够增加肠道抑食性食欲激素GLP-1、PYY水平进而减少T2DM大鼠摄食量,其作用机制可能与大枣减轻T2DM大鼠肠道炎症,修复肠道损伤,恢复肠道激素的分泌有关.
Abstract
Objective:To investigate the effects and underlying mechanisms of jujube on feeding behavior and intestinal inflammatory injury in rats with type 2 diabetes mellitus(T2DM).Methods:SD rats were randomly assigned to four groups:a blank control group,a T2DM model group,a low-dose jujube group(1.575 g/kg),and a high-dose jujube group(9.45 g/kg).Apart from the blank group,rats in the remaining groups were subjected to a high-fat,high-sugar diet combined with streptozotocin(STZ)administration to induce the T2DM model.Following successful model establishment,rats in the jujube groups received daily gavage with different concentrations of jujube solution for 4 consecutive weeks.General conditions,food intake,and blood glucose levels were monitored and recorded.Additionally,serum levels of inflammatory factors including interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),glucagon-like peptide-1(GLP-1),and peptide YY(PYY)were assayed.Histopathological analysis of the ileum was performed to assess tissue damage and cell apoptosis,and the expressions of inflammation-and apoptosis-related genes such as nuclear factor NF-κB p65(NF-κB p65)and cysteine-aspartic acid protease-3(Caspase3),as well as related proteins including Toll-like receptor 4(TLR4),NF-κB p65,phosphorylated NF-κB p65(p-NF-κB p65),BCL2-associated X protein(Bax),B-cell lymphoma-2(Bcl-2),Pro Caspase3,and Cleaved Caspase3 were measured in the intestinal tissue.Results:Compared with the model group,the rats in the administration group exhibited a highly significant reduction in food intake(P＜0.01).Serum levels of TNF-α and IL-1βwere significantly decreased(P＜0.01),while GLP-1 levels were markedly elevated(P＜0.01).Notably,PYY levels showed a highly significant increase in the high-dose jujube group(P＜0.01).Additionally,the inflammatory injury in ileal tissue improved,with a significant reduction in the apoptosis rate of ileal cells in the high-dose jujube group(P＜0.01).Furthermore,the expression levels of intestinal NF-κB p65,Caspase3 mRNA,as well as NF-κB p65 and Cleaved Caspase3 proteins were significantly downregulated in the administration group(P＜0.05,P＜0.01).Additionally,the high-dose jujube group exhibited significant downregulation of p-NF-κB p65,Pro Caspase3,and the Bax/Bcl-2 protein ratio(P＜0.05,P＜O.0l).Conclusion:Jujube has the potential to elevate intestinal anorexigenic hormones GLP-1 and PYY,thereby reducing food intake in T2DM rats.This effect may be mediated through jujube's ability to alleviate intestinal inflammation,repair intestinal damage,and restore intestinal hormone secretion in T2DM rats.
维普
万方数据