Effects of acupuncture on podocyte autophagy and the LncRNA SOX2OT/mTORC1/ULK1 pathway in rats with diabetic kidney disease

WANG Xu; ZHANG Yue; LI Hongwei; LIU Handong; LI Jie; FAN Ying; ZHANG Zhilong

doi:10.13703/j.0255-2930.20240827-k0004

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Effects of acupuncture on podocyte autophagy and the LncRNA SOX2OT/mTORC1/ULK1 pathway in rats with diabetic kidney disease

Study on Mechanism | 更新时间：2025-10-11

- Effects of acupuncture on podocyte autophagy and the LncRNA SOX2OT/mTORC1/ULK1 pathway in rats with diabetic kidney disease
- Chinese Acupuncture & Moxibustion Vol. 45, Issue 10, Pages: 1450-1458(2025)
- 作者机构：
  
  天津市中医药研究院附属医院针灸科，天津　300120
  天津市华苑街社区卫生服务中心中医科
  郑州大学第五附属医院中医二科
- 作者简介：
- 基金信息：
- DOI：10.13703/j.0255-2930.20240827-k0004
  CLC：
- Received：27 August 2024，
  
  Online First：30 July 2025，
  
  Published：12 October 2025
- 稿件说明：
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WANG Xu, ZHANG Yue, LI Hongwei, et al. Effects of acupuncture on podocyte autophagy and the LncRNA SOX2OT/mTORC1/ULK1 pathway in rats with diabetic kidney disease[J]. Chinese Acupuncture & Moxibustion, 2025, 45(10): 1450-1458.
DOI：

WANG Xu, ZHANG Yue, LI Hongwei, et al. Effects of acupuncture on podocyte autophagy and the LncRNA SOX2OT/mTORC1/ULK1 pathway in rats with diabetic kidney disease[J]. Chinese Acupuncture & Moxibustion, 2025, 45(10): 1450-1458. DOI： 10.13703/j.0255-2930.20240827-k0004.

摘要

目的：

观察针刺对糖尿病肾病（DKD）大鼠足细胞自噬及长链非编码核糖核酸性别决定相关基因簇2重叠转录本（LncRNA SOX2OT）/雷帕霉素靶蛋白C1（mTORC1）/Unc-51样激酶1（ULK1）通路的影响，探究针刺降低尿蛋白的作用机制。

方法：

将40只SPF级雄性SD大鼠随机分为空白组（10只）和造模组（30只）。造模组以高脂高糖饲料喂养联合腹腔注射链脲佐菌素（STZ）溶液方法建立DKD大鼠模型。将造模成功的20只大鼠随机分为针刺组和模型组，各10只。针刺组采用调理脾胃针法干预，穴取双侧“足三里”“丰隆”“阴陵泉”及“中脘”，每次30 min，每日1次，每周5次，共干预4周。比较各组大鼠干预前后一般情况、空腹血糖（FBG）、餐后2 h血糖（2hPG）、血肌酐（SCr）、血尿素氮（BUN）、24 h尿蛋白定量和尿液蛋白含量/血肌酐比率（UACR）；干预后，采用ELISA法检测大鼠尿液足细胞损伤标志物（SPON2）水平，透射电镜观察大鼠肾组织足细胞自噬体和基底膜超微结构，TUNEL染色观察肾组织足细胞凋亡情况，Western blot法检测肾组织微管相关蛋白1轻链3-Ⅱ（LC3-Ⅱ）、mTORC1、ULK1、自噬调控蛋白（Beclin-1）、螯合体1（p62）蛋白表达，实时荧光定量PCR法检测大鼠肾组织LncRNA SOX2OT表达。

结果：

干预后，与空白组比较，模型组大鼠出现食水摄入量、小便量增加并伴形体消瘦，大便稀溏等；与模型组比较，针刺组大鼠食水摄入量、小便量、大便溏稀等改善明显。与空白组比较，模型组大鼠FBG、2hPG、SCr、BUN、24小时尿蛋白定量、UACR、尿液SPON2升高（

0.01）；与模型组比较，针刺组大鼠FBG、2hPG、SCr、BUN、24小时尿蛋白定量、UACR、尿液SPON2降低（

0.01）。与空白组比较，模型组大鼠肾组织足细胞自噬小体减少、基底膜增厚；与模型组比较，针刺组足细胞自噬小体增多、基底膜增厚减轻。与空白组比较，模型组大鼠足细胞凋亡指数（AI）升高（

0.01）；与模型组比较，针刺组大鼠足细胞AI降低（

0.01）。与空白组比较，模型组大鼠ULK1、Beclin-1、LC3-Ⅱ蛋白表达降低（

0.01），mTORC1、p62蛋白表达升高（

0.01）；与模型组比较，针刺组大鼠ULK1、Beclin-1、LC3-Ⅱ蛋白表达升高（

0.01），mTORC1、p62蛋白表达降低（

0.01）。与空白组比较，模型组大鼠LncRNA SOX2OT表达降低（

0.01）；与模型组比较，针刺组LncRNA SOX2OT表达升高（

0.01）。

结论：

调理脾胃针法可改善DKD大鼠肾功能，降低血糖及尿蛋白排泄，减轻足细胞损伤，提高足细胞自噬水平，其机制可能与调节肾脏LncRNA SOX2OT/mTORC1/ULK1通路相关。

Abstract

Objective

To observe the effects of acupuncture on podocyte autophagy and long non-coding RNA SOX2 overlapping transcript (LncRNA SOX2OT)/mammalian target of rapamycin C1 (mTORC1)/Unc-51-like kinase 1 (ULK1) pathway in rats with diabetic kidney disease (DKD)

and to explore the mechanism by which acupuncture reduces urinary protein.

Methods

A total of 40 SPF-grade male Sprague-Dawley rats were randomly divided into a control group (

=10) and a modeling group (

=30). The DKD model was established by feeding a high-fat

high-sugar diet combined with intraperitoneal injection of streptozotocin (STZ) in the modeling group. Twenty rats with successful DKD model were randomly divided into a model group (

=10) and an acupuncture group (

=10). The acupuncture group received "spleen and stomach-regulating" acupuncture at bilateral "Zusanli" (ST36)

"Fenglong" (ST40)

"Yinlingquan" (SP9)

and "Zhongwan" (CV12)

30 min per session

once daily

five times per week

for four weeks. The general condition

fasting blood glucose (FBG)

2-hour postprandial glucose (2hPG)

serum creatinine (SCr)

blood urea nitrogen (BUN)

24-hour urinary protein quantification

and urine albumin-to-creatinine ratio (UACR) were compared before and after the intervention. After intervention

urinary podocyte injury marker SPON2 was measured by ELISA. Podocyte autophagosomes and glomerular basement membrane ultrastructure in renal tissue were observed via transmission electron microscopy. Podocyte apoptosis was assessed by TUNEL staining. The protein expression of microtubule-associated protein 1 light chain 3Ⅱ (LC3-Ⅱ)

mTORC1

ULK1

Beclin-1

and p62 in renal tissue was detected by Western blot. LncRNA SOX2OT expression in renal tissue was measured by real-time PCR.

Results

After the intervention

compared with the control group

the model group exhibited increased food and water intake

increased urine output

weight loss

and loose stools; compared with the model group

the food and water intake

urine volume

and loose stools were improved in the acupuncture group. Compared with the control group

FBG

2hPG

SCr

BUN

24-hour urinary protein quantification

UACR

and urinary SPON2 were all higher in the model group (

0.01); compared with the model group

the FBG

2hPG

SCr

BUN

24-hour urinary protein quantification

UACR

and urinary SPON2 were all lower in the acupuncture group (

0.01). Compared with the control group

the model group showed reduced podocyte autophagosomes and thickened glomerular basement membrane; compared with the model group

the acupuncture group had increased podocyte autophagosomes and less thickened basement membrane. Compared with the control group

the podocyte apoptosis index (AI) was higher in the model group (

0.01); compared with the model group

the AI was lower in the acupuncture group (

0.01). Compared with the control group

the expression of ULK1

Beclin-1

and LC3-Ⅱ proteins was lower

and the expression of mTORC1 and p62 proteins was higher in the model group (

0.01). Compared with the model group

the expression of ULK1

Beclin-1

and LC3-Ⅱ proteins was higher

and the expression of mTORC1 and p62 proteins was lower in the acupuncture group (

0.01). Compared with the control group

the LncRNA SOX2OT expression was lower in the model group (

0.01). Compared with the model group

LncRNA SOX2OT expression was higher in the acupuncture group (

0.01).

Conclusion

The "spleen and stomach-regulating" acupuncture method could improve renal function in DKD rats

reduce blood glucose and urinary protein excretion

alleviate podocyte injury

and enhance podocyte autophagy. The mechanism may be related to modulation of the renal LncRNA SOX2OT/mTORC1/ULK1 pathway.

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