文献类型：期刊文献

中文题名：红芪多糖对糖尿病胃轻瘫大鼠胃窦组织平滑肌细胞焦亡的影响

英文题名：Effects of Hedysarum Polybotrys Polysacchcaide on Pyroptosis of Smooth Muscle Cells in Gastric Antrum Tissue of Diabetic Gastroparesis Rats

作者：仲倩利[1];李荣科[1];万生芳[1];张倩[1];魏昭晖[1];郭倩[1];马欣欣[1];张磊[1];杨雅丽[1];张亚男[1]

第一作者：仲倩利

机构：[1]甘肃中医药大学,甘肃兰州730000

第一机构：甘肃中医药大学

年份：2023

卷号：30

期号：11

起止页码：100

中文期刊名：中国中医药信息杂志

外文期刊名：Chinese Journal of Information on Traditional Chinese Medicine

收录：CSTPCD;;CSCD:【CSCD_E2023_2024】；

基金：国家自然科学基金(82060914);甘肃省中医药研究中心开放课题(zyzx-2020-zx112);甘肃中医药大学中医学一级学科“岐黄英才”导师专项基金(2022年)。

语种：中文

中文关键词：糖尿病胃轻瘫;红芪多糖;细胞焦亡;NOD样受体蛋白3;胱天蛋白酶-1;大鼠

外文关键词：diabetic gastroparesis;Hedysarum Polybotrys polysacchcaide;pyroptosis;NLRP3;Caspase-1;rats

摘要：目的以胃窦组织平滑肌细胞焦亡为切入点,探讨红芪多糖干预糖尿病胃轻瘫(DGP)的作用机制。方法60只SPF级雄性Wistar大鼠随机选取10只为空白组,其余50只采用一次性大剂量腹腔注射链脲佐菌素联合高脂高糖饲料不规则喂养制备DGP模型。将成模大鼠随机分为模型组、莫沙必利组和红芪多糖低、中、高剂量组。莫沙必利组予枸橼酸莫沙必利分散片3.5mg/kg灌胃,红芪多糖低、中、高剂量组分别予红芪多糖50、100、200 mg/kg灌胃,空白组和模型组予等体积纯净水灌胃,每日1次,连续8周。检测大鼠随机血糖及体质量,测定胃排空率;HE染色观察胃窦组织病理形态;TUNEL染色检测胃窦组织平滑肌细胞DNA损伤情况;RT-qPCR和Western blot检测胃窦组织NOD样受体蛋白3(NLRP3)、胱天蛋白酶-1(Caspase-1)、焦孔素D(GSDMD)和白细胞介素-1β(IL-1β)mRNA和蛋白表达。结果与空白组比较,模型组大鼠各时点随机血糖显著升高(P<0.01),体质量、胃排空率显著降低(P<0.01),胃窦组织平滑肌细胞胞膜完整性丧失,大面积黏膜上皮细胞坏死脱落,有大量炎性细胞浸润,细胞损伤率显著升高(P<0.01),NLRP3、Caspase-1、GSDMD、IL-1βmRNA和蛋白表达显著升高(P<0.05,P<0.01);与模型组比较,各给药组大鼠给药8周后随机血糖显著降低(P<0.01),体质量、胃排空率显著升高(P<0.01),胃窦组织NLRP3、Caspase-1、GSDMD、IL-1βmRNA和蛋白表达显著降低(P<0.05,P<0.01),红芪多糖中、高剂量组和莫沙必利组胃窦组织平滑肌细胞损伤率显著降低(P<0.05,P<0.01),黏膜损伤和炎性细胞浸润有不同程度缓解。结论红芪多糖可改善胃动力、促进胃排空、缓解DGP进程,其机制可能与抑制胃窦组织平滑肌细胞焦亡有关。
Objective To investigate the mechanism of Hedysarum Polybotrys polysacchcaide(HPS)on diabetic gastroparesis(DGP)by taking the pyroptosis of smooth muscle cells in gastric antrum tissue as the breakthrough point.Methods 10 of the 60 SPF grade male Wistar rats were randomly selected as the blank group,and the remaining 50 rats were given a one-time high dose intraperitoneal injection of streptozotocin combined with a high fat and high sugar diet irregular feeding to establish a DGP model.The model rats were randomly divided into model group,mosapride group and HPS low-,medium-and high-dosage groups.The mosapride group was given 3.5 mg/kg mosapride by gavage,the HPS low-,medium-and high-dosage groups were given 50,100 and 200 mg/kg HPS solution by gavage,and the blank group and model group were given the same volume of purified water by gavage once a day for 8 weeks.Random blood glucose,body mass and gastric emptying rate were measured;HE staining was used to observe the pathological morphology of gastric antrum tissue;TUNEL staining was used to detect the DNA damage of smooth muscle cells in gastric antrum tissue;the mRNA and protein expression of NOD-like receptor pyrin domain-containing protein 3(NLRP3),Caspase-1,gasdermin D(GSDMD)and interleukin-1β(IL-1β)in gastric antrum tissue were detected by RT-qPCR and Western blot.Results Compared with the blank group,the random blood glucose of rats in the model group at each time point increased significantly(P<0.01),the body mass and gastric emptying rate decreased significantly(P<0.01);smooth muscle cells in gastric antrum tissue showed a loss of cell membrane integrity,large areas of mucosal epithelial cells were necrotic and exfoliated,a large number of inflammatory cells were infiltrated,cell damage rate significantly increased(P<0.01),and NLRP3,Caspase-1,GSDMD,IL-1βmRNA and protein expression significantly increased(P<0.05,P<0.01).Compared with the model group,the random blood glucose of rats in each administration group significantly decreased after 8 weeks of administration(P<0.01),the body mass and gastric emptying rate significantly increased(P<0.01),the mRNA and protein expressions of NLRP3,Caspase-1,GSDMD,and IL-1βin gastric antrum tissue significantly decreased(P<0.05,P<0.01),cell damage rate of smooth muscle cells in gastric antrum tissue of HPS medium-and high-dosage group and mosapride group decreased significantly(P<0.05,P<0.01),mucosal damage and inflammatory cell infiltration were alleviated to varying degrees.Conclusion HPS can improve gastric motility,promote gastric emptying and alleviate DGP process,and the mechanism may be related to the inhibition of smooth muscle cell pyroptosis in gastric antrum tissue.