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周钰, 刘一凡, 姜维娜, 宫成军.益元饮通过下调TGF-β1/PI3K/Akt信号通路治疗糖尿病肾病的作用机制[J].湖南中医药大学学报,2026,46(3):490-498[点击复制] |
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| 益元饮通过下调TGF-β1/PI3K/Akt信号通路治疗糖尿病肾病的作用机制 |
| 周钰,刘一凡,姜维娜,宫成军 |
| (辽宁中医药大学, 辽宁 沈阳 110032;辽宁中医药大学附属医院, 辽宁 沈阳 110032) |
| 摘要: |
| 目的 探讨益元饮通过调节转化生长因子-β1（TGF-β1）/磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（Akt）信号通路治疗糖尿病肾病的作用机制。方法 75只SPF级雄性Wistar大鼠随机分为5组，包括正常组、模型组、益元饮组（23.52 g·kg-1·d-1）、胰激肽原酶片组（36 U·kg-1·d-1)、真武汤组（4.2 g·kg-1·d-1），每组15只。除正常组外,其余通过高糖高脂饮食喂养4周后，联合腹腔注射链脲佐菌素（STZ）（30 mg·kg-1·d-1）构建糖尿病肾病大鼠模型，连续干预8周。观察各组大鼠的一般情况；HE与Masson染色观察肾脏组织病理改变；记录各组大鼠随机血糖（GLU）、24 h尿蛋白定量(24 hUTP)、尿白蛋白/肌酐（UACR）；Western blot检测肾组织TGF-β1、PI3K、Akt、磷酸化PI3K（p-PI3K）、磷酸化Akt（p-Akt）及纤维连接蛋白（FN）的表达水平。结果 正常组大鼠一般情况良好，精神、饮食、活动、饮水量与排泄量正常；模型组大鼠精神萎靡，毛发光泽差，出现多饮、多食、多尿症状；益元饮组大鼠精神状态、活动度、对外界刺激应答等表现有显著恢复，饮水量与尿量较模型组减少，体重稳定增长；胰激肽原酶片组大鼠精神状态及活动度等表现恢复较好，真武汤组大鼠精神较活跃，但仍嗜卧倦怠，对外界刺激反应较为迟滞。正常组大鼠肾小球形态规整，肾间质仅见少量蓝染胶原纤维；模型组第8周出现肾脏肾小球系膜基质显著增生，肾小管上皮细胞水肿，肾间质胶原纤维大量沉积；真武汤组恢复效果居中；益元饮组及胰激肽原酶片组，肾小球和肾小管形态恢复较好，肾间质纤维化程度明显下降。与正常组比较，模型组大鼠体质量降低（P<0.05）、GLU升高（P<0.05）、24 hUTP水平升高（P<0.05）、UACR水平升高（P<0.05），肾组织中TGF-β1、p-PI3K、p-Akt和FN蛋白表达上调（P<0.01）。与模型组比较，各治疗组体质量有所增加（P<0.05），肾脏肥大指数均降低（P<0.05）,24 hUTP水平、UACR水平均下降（P<0.05），且各治疗组均能显著抑制TGF-β1的表达（P<0.01），并降低PI3K、Akt的磷酸化水平（P<0.05，P<0.01），同时下调FN蛋白表达水平（P<0.05，P<0.01）。与真武汤组比较，胰激肽原酶片组24 hUTP水平、UACR水平均下降（P<0.05）；益元饮组体质量升高（P<0.05），24 hUTP水平、UACR水平均下降（P<0.05）。益元饮组上述指标改善程度与胰激肽原酶片组相当（P>0.05）。结论 益元饮能够降低DKD大鼠的血糖水平、改善肾功能、改善肾脏病理损伤，延缓DKD进程，其作用机制可能与抑制TGF-β1/PI3K/Akt信号通路激活有关。 |
| 关键词: 糖尿病肾病 肾纤维化 益元饮 转化生长因子-β1/磷脂酰肌醇3激酶/蛋白激酶B信号通路 链脲佐菌素 |
| DOI：10.3969/j.issn.1674-070X.2026.03.008 |
| 投稿时间：2025-12-01 |
| 基金项目:辽宁省教育厅2023年度高等学校基本科研项目（JYTMS20231818）；第五批全国中医临床优秀人才研修项目（国中医药人教函〔2022〕1号）；全国名老中医药专家传承工作室建设项目（国中医药人教函〔2022〕75号）。 |
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| Mechanism of action of Yiyuan Drink in treating diabetic kidney disease by down-regulating the TGF-β1/PI3K/Akt signaling pathway |
| ZHOU Yu, LIU Yifan, JIANG Weina, GONG Chengjun |
| (Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning 110032, China;The First Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning 110032, China) |
| Abstract: |
| Objective To investigate the mechanism of action by which Yiyuan Drink treats diabetic kidney disease (DKD) by regulating the transforming growth factor-β1 (TGF-β1)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Methods Seventy-five SPF male Wistar rats were randomly divided into five groups: control group, model group,Yiyuan Drink group (23.52 g·kg-1·d-1), pancreatic kininogenase tablets group (36 U·kg-1·d-1), and Zhenwu Decoction group (4.2 g·kg-1·d-1), with 15 rats in each group. Except for the control group, the remaining rats were fed with a high-sugar and high-fat diet for 4 weeks, followed by intraperitoneal injection of streptozotocin (STZ, 30 mg·kg-1·d-1) to establish the DKD model. Treatments were administered for 8 successive weeks. The general conditions of rats in each group were observed. Renal histopathological changes were examined by HE and Masson staining. Random blood glucose (GLU), 24-hour urinary protein (24 hUTP), and urinary albumin-to-creatinine ratio (UACR) in each group were measured. Western blot analysis was performed to test the expression levels of TGF-β1, PI3K, Akt, phosphorylated PI3K (p-PI3K), phosphorylated Akt (p-Akt), and fibronectin (FN) in renal tissues. Results Rats in the control group exhibited good overall conditions, including normal mental state, appetite, activity levels, water intake, and excretion. Rats in the model group exhibited lethargy, lusterless hair, and polydipsia, polyphagia, and polyuria. Rats in the Yiyuan Drink group showed significant improvement in mental state, activity levels, and responses to external stimuli; their water intake and urine output were reduced compared to the model group, and their body weight increased steadily. Rats in the kininogenase tablet group showed relatively good recovery in mental state and activity levels. Rats in the Zhenwu Decoction group were relatively active but still exhibited a tendency to lie down and appeared lethargic, with sluggish responses to external stimuli. Histopathological examination revealed that rats in the control group had regular glomerular morphology and minimal collagen deposition in the renal interstitium. In contrast, rats in the model group showed marked mesangial matrix proliferation, tubular epithelial cell edema, and massive collagen deposition in the renal interstitium by week 8. The Zhenwu Decoction group showed moderate recovery, while the Yiyuan Drink and the pancreatic kininogenase tablets groups showed improved renal morphology and reduced renal interstitial fibrosis. Compared with the control group, rats in the model group exhibited reduced body weight (P<0.05), elevated GLU levels (P<0.05), increased 24-hUTP levels (P<0.05), and elevated UACR (P<0.05), along with significantly upregulated expressions of TGF-β1, p-PI3K, p-Akt, and FN (P<0.01) in renal tissues. Compared with the model group, all treatment groups exhibited increased body weight (P<0.05), decreased renal hypertrophy index (P<0.05), reduced 24-h UTP and UACR levels (P<0.05). Furthermore, all treatment groups significantly suppressed TGF-β1 expression (P<0.01) and reduced the phosphorylation levels of PI3K and Akt (P<0.05, P<0.01), while simultaneously downregulating the expression levels of the FN protein (P<0.05, P<0.01). Compared with the Zhenwu Decoction group, the pancreatic kininogenase tablets group showed decreased levels of 24-h UTP and UACR (P<0.05). In the Yiyuan Drink group, body weight increased (P<0.05), while the levels of 24-h UTP and UACR were reduced (P<0.05). The degree of improvement in the aforementioned indicators in the Yiyuan Drink group was comparable to that in the Pancreatin kininogenase tablets group (P>0.05). Conclusion Yiyuan Drink can reduce GLU levels, improve renal function, and alleviate pathological damage in DKD rats, thereby delaying the progression of DKD. Its underlying mechanism of action may be related to inhibiting the activation of the TGF-β1/PI3K/Akt signaling pathway. |
| Key words: diabetic kidney disease renal fibrosis Yiyuan Drink TGF-β1/PI3K/Akt signaling pathway streptozotocin |
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