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基于Wnt7a/GSK-3β信号轴探讨左归丸改善妊娠糖尿病大鼠子代胰腺β细胞功能的机制
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| 篇名： | 基于Wnt7a/GSK-3β信号轴探讨左归丸改善妊娠糖尿病大鼠子代胰腺β细胞功能的机制 |
| TITLE： | Mechanism of Zuogui pill in improving pancreatic β cell function in offspring of rats with gestational diabetes mellitus based on Wnt7a/GSK-3β signaling axis |
| 摘要： | 目的 研究左归丸改善妊娠糖尿病（GDM）大鼠子代胰腺β细胞功能的机制。方法将36只孕鼠分为正常组、模型组、甘精胰岛素组（阳性对照）和左归丸低、中、高剂量组，每组6只。正常组和模型组灌胃等体积生理盐水；甘精胰岛素组按初始剂量1U/kg皮下注射甘精胰岛素，次日以1U为单位逐日增加药量，直至随机血糖正常；左归丸低、中、高剂量组分别灌胃4.725、9.45、18.9g/kg左归丸药液，每日1次，直至子鼠出生。在子鼠出生后第21天（每组取12只子鼠），检测其体重、空腹血糖（FBG）并进行口服葡萄糖耐量实验。观察出生后60d子鼠的胰腺组织病理变化；检测其胰腺组织中胰岛素阳性表达面积比，血清中糖化血清蛋白（GSP）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）含量，胰腺组织中无翅型小鼠乳腺肿瘤病毒整合位点家族成员7a（Wnt7a）、糖原合成酶激酶3β（GSK-3β）的mRNA和蛋白相对表达量。结果与正常组比较，模型组子鼠体重、胰腺组织中胰岛素阳性表达面积比、血清中HDL-C含量以及胰腺组织中Wnt7a的mRNA和蛋白相对表达量均显著降低（P＜0.05）；FBG，灌胃20%葡萄糖溶液后60、90、120min的血糖水平，血清中GSP、LDL-C含量，以及胰腺组织中GSK-3β的mRNA和蛋白相对表达量均显著升高（P＜0.05）；胰腺组织可见胰岛细胞轻度变性、坏死。与模型组比较，左归丸中、高剂量组子鼠上述指标均显著逆转（P＜0.05），胰腺组织病理损伤不同程度改善。结论左归丸可能通过恢复Wnt7a/GSK-3β信号轴稳态，改善GDM大鼠子代的胰腺β细胞功能。 |
| ABSTRACT： | OBJECTIVE To investigate the mechanism of Zuogui pill in improving pancreatic β cell function in the offspring of rats with gestational diabetes mellitus （GDM）.METHODS Thirty-six pregnant rats were divided into normal group， model group， insulin glargine group （positive control）， and low-， medium- and high-dose Zuogui pill groups， with 6 rats in each group. The normal group and model group were given intragastric administration of equal-volume normal saline. The insulin glargine group was subcutaneously injected with insulin glargine at an initial dose of 1 U/kg， and the dosage was increased by 1 U per day until random blood glucose returned to normal. The low-， medium- and high-dose Zuogui pill groups were intragastrically administered with Zuogui pill solutions at 4.725， 9.45 and 18.9 g/kg once a day until the birth of offspring. On postnatal day 21 （12 offspring in each group）， body weight， fasting blood glucose （FBG） and oral glucose tolerance test were performed on the offspring. Pancreatic histopathological changes of 60-day-old offspring were observed. The insulin-positive expression area ratio in pancreatic tissue， serum levels of glycated serum protein （GSP）， high-density lipoprotein cholesterol （HDL-C） and low-density lipoprotein cholesterol （LDL-C）， as well as the mRNA and protein relative expression levels of wingless-type MMTV integration site family member 7a（Wnt7a）and glycogen synthase kinase 3β（GSK-3β） in pancreatic tissue were detected.RESULTS Compared with normal group， the body weight， insulin-positive expression area ratio in pancreatic tissue， serum HDL-C level， and the mRNA and protein relative expression levels of Wnt7a in pancreatic tissue were significantly decreased of the offspring in the model group （ P ＜0.05）. Meanwhile， FBG， blood glucose levels at 60， 90 and 120 min after intragastric administration of 20% glucose solution， serum GSP and LDL-C levels， as well as the mRNA and protein relative expression levels of GSK-3β in pancreatic tissue were significantly increased （ P ＜0.05）；mild degeneration and necrosis of islet cells were observed in pancreatic tissue. Compared with the model group， the above-mentioned indexes were significantly reversed in medium- and high-dose Zuogui pill groups （ P ＜0.05）， and pancreatic pathological injury was improved to varying degrees.CONCLUSIONS Zuogui pill may restore the homeostasis of Wnt7a/GSK-3β signaling axis， so as to improve pancreatic β cell function in the offspring of GDM rats. |
| 期刊： | 2026年第37卷第17期 |
| 作者： | 张紫薇；孙凯男；彭思其；许凯霞；王永辉；王超群 |
| AUTHORS： | ZHANG Ziwei，SUN Kainan，PENG Siqi，XU Kaixia，WANG Yonghui，WANG Chaoqun |
| 关键字： | 左归丸；妊娠糖尿病；子代胰腺功能障碍；Wnt7a；GSK-3β |
| KEYWORDS： | gestational diabetes mellitus;pancreatic dysfunction in offspring;Wnt7a;GSK-3β |
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