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左归丸胚胎期干预对妊娠糖尿病孕鼠子代糖耐量的影响及机制
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| 篇名： | 左归丸胚胎期干预对妊娠糖尿病孕鼠子代糖耐量的影响及机制 |
| TITLE： | Effect and mechanism of embryonic intervention with Zuogui pill on the glucose tolerance in offsprings of pregnant rats with gestational diabetes mellitus |
| 摘要： | 目的 探讨左归丸胚胎期干预对妊娠糖尿病孕鼠子代糖耐量的影响及机制。方法将孕鼠随机分为空白组、模型组、阳性对照组（甘精胰岛素）和左归丸低、中、高剂量组（4.725、9.45、18.9g/kg），除空白组外，其余各组孕鼠腹腔注射链脲佐菌素制备妊娠糖尿病模型，妊娠6～18d时各组孕鼠灌胃相应药物和蒸馏水，每日1次。子鼠出生21d时，记录体重和体长，通过糖耐量试验计算曲线下面积（AUC）。子鼠出生22d时，检测空腹血糖（FBG）和空腹胰岛素（FINS）、胰岛素敏感指数（ISI）、稳态模型评估胰岛素抵抗指数（HOMA-IR），观察胰腺组织形态结构；运用串联质谱标签蛋白质组学分析胰腺组织的蛋白谱，并检测载脂蛋白A1（ApoA1）、溶质载体家族27成员1（Slc27a1）、激肽原1（Kng1）、钠钾ATP酶α2亚基（Atp1a2）、溶质载体家族7成员5（Slc7a5）、溶质载体家族3成员2（Slc3a2）、胆汁酸辅酶A：氨基酸N-酰基转移酶（Baat）、真核翻译起始因子2亚基γ（Eif2s3）蛋白及mRNA表达水平。结果与模型组比较，阳性对照组和左归丸中剂量组子鼠体重、体长、ISI均显著增加/升高（P＜0.05），糖耐量和胰岛细胞增生均明显改善，AUC、FBG、FINS、HOMA-IR均显著降低（P＜0.05）。左归丸胚胎期干预妊娠糖尿病孕鼠子代的潜在靶蛋白有88个，涉及过氧化物酶体增殖物激活受体（PPAR）、环磷酸鸟苷-蛋白激酶G（cGMP-PKG）、脂肪消化和吸收、胆汁分泌等多条通路，与糖代谢和胰岛素抵抗等关系密切的蛋白主要有ApoA1、Slc27a1、Kng1、Atp1a2、Slc7a5、Slc3a2、Baat、Eif2s3。其中，与模型组比较，左归丸中剂量组孕鼠子代胰腺组织中Slc7a5、Slc3a2、Baat蛋白及mRNA表达量均显著上调（P＜0.05），ApoA1、Slc27a1、Kng1、Atp1a2、Eif2s3蛋白及mRNA表达量均显著下调（P＜0.05）。结论左归丸胚胎期干预能改善GDM孕鼠子代的血糖水平和胰腺病理形态，其机制可能与上调PPAR、cGMP-PKG、脂肪消化和吸收、胆汁分泌等通路中的Slc7a5、Slc3a2、Baat表达，下调ApoA1、Slc27a1、Kng1、Atp1a2、Eif2s3表达有关。 |
| ABSTRACT： | OBJECTIVE To explore the effect and mechanism of embryonic intervention with Zuogui pill on the glucose tolerance in offsprings of pregnant rats with gestational diabetes mellitus. METHODS Pregnant rats were randomly divided into blank group， model group， positive control group （insulin glargine）， Zuogui pill low-， medium- and high-dose groups （4.725， 9.45， 18.9 g/kg）. In addition to the blank group， streptozotocin was injected intraperitoneally to establish a gestational diabetes mellitus rat model. From day 6 to day 18 of pregnancy， each group was given relevant medicine and distilled water intragastrically， once a day. After 21 days of birth， the body weight and body length of offsprings were recorded， and the area under the curve （AUC） was calculated through a glucose tolerance test. After 22 days of birth， fasting blood glucose （FBG）， fasting insulin （FINS） levels in serum， insulin sensitivity index （ISI）， and homeostasis model assessment of insulin resistance （HOMA-IR） were measured， and the morphological structure of pancreatic tissue was observed. The protein spectrum of pancreatic tissue was analyzed by tandem mass tag-based proteomics， and protein and mRNA expression levels of apolipoprotein A1（ApoA1）， solute carrier family 27 member 1 （Slc27a1）， kininogen 1（Kng1） and sodium/potassium-transporting ATPase subunit alpha 2 （Atp1a2）， solute carrier family 7 member 5 （Slc7a5）， solute carrier family 3 member 2 （Slc3a2）， bile acid-coenzyme A： amino acid N- acyltransferase （Baat）， eukaryotic translation initiation factor 2 subunit gamma （Eif2s3） were detected. RESULTS Compared with the model group， the body weight， body length and ISI of offsprings in the positive control group and Zuogui pill medium-dose group were significantly increased （P＜0.05）， while the glucose tolerance and islet cell proliferation were significantly improved， and the AUC， FBG， FINS and HOMA-IR were significantly decreased （P＜0.05）. There were 88 potential target proteins for the embryonic intervention of Zuogui pill in offsprings of pregnant rats with gestational diabetes mellitus，involving multiple pathways such as peroxisome proliferator-activated receptor （PPAR）， cyclic guanosine monophosphate-protein kinase G （cGMP-PKG）， fat digestion and absorption， and bile secretion. The proteins closely related to glucose metabolism and insulin resistance mainly included ApoA1， Slc27a1， Kng1， Atp1a2， Slc7a5， Slc3a2， Baat， and Eif2s3. Among them， compared with the model group， protein and mRNA expressions of Slc7a5， Slc3a2， and Baat in the pancreatic tissues of pregnant rat offsprings in the Zuogui pill medium-dose group were significantly up-regulated （P＜0.05）； protein and mRNA expressions of ApoA1， Slc27a1， Kng1， Atp1a2 and Eif2s3 were all significantly down-regulated （P＜0.05）. CONCLUSIONS The intervention of Zuogui pill in the embryonic period on offsprings of pregnant rats with gestational diabetes mellitus can improve their blood glucose levels and pancreatic pathological morphology. The mechanism may be related to the upregulation of the expressions of Slc7a5， Slc3a2， and Baat and the down-regulation of ApoA1， Slc27a1， Kng1， Atp1a2 and Eif2s3 expressions in the PPAR， cGMP-PKG， fat digestion and absorption， and bile secretion pathways. |
| 期刊： | 2025年第36卷第16期 |
| 作者： | 杨敏；吴玉洁；孙凯男；王永辉；王超群；许凯霞 |
| AUTHORS： | YANG Min，WU Yujie，SUN Kainan，WANG Yonghui，WANG Chaoqun，XU Kaixia |
| 关键字： | 左归丸；妊娠糖尿病；子代发育；TMT蛋白组学 |
| KEYWORDS： | Zuogui pill； gestational diabetes mellitus； offspring development； TMT proteomics |
| 阅读数： | 5 次 |
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