CHEN Yanxu,JIN Caiyun,JIN Zhisheng,et al.Mechanism of Hedysarum Polysaccharide in Diabetic Nephropathy in db/db Mice Based on Wnt/β-catenin Signal Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(21):74-80.
CHEN Yanxu,JIN Caiyun,JIN Zhisheng,et al.Mechanism of Hedysarum Polysaccharide in Diabetic Nephropathy in db/db Mice Based on Wnt/β-catenin Signal Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(21):74-80. DOI: 10.13422/j.cnki.syfjx.20221939.
Mechanism of Hedysarum Polysaccharide in Diabetic Nephropathy in db/db Mice Based on Wnt/β-catenin Signal Pathway
治疗12周后,与正常组比较,模型组小鼠一般状态较差且肾脏组织病理超微结构病变显著,其GLU、24 h UTP、SCr、BUN水平均升高(
P
<
0.01);与模型组比较,HPS高、中剂量组小鼠一般状态及肾脏组织病理超微结构均得到一定程度改善,其GLU、24 h UTP、SCr、BUN水平均降低(
P
<
0.05,
P
<
0.01);与正常组比较,模型组Wnt1、
β
-catenin、GSK-3
β
及p-GSK-3
β
mRNA及蛋白表达水平均升高(
P
<
0.01);与模型组比较,HPS高、中剂量组Wnt1、
β
-catenin、GSK-3
β
及p-GSK-3
β
mRNA及蛋白表达水平均明显降低(
P
<
0.05,
P
<
0.01)。
结论
2
HPS可在一定程度上减轻糖尿病肾病的肾损伤,其机制可能与抑制Wnt/
β
-catenin信号通路激活有关。
Abstract
Objective
2
To observe the effect of Hedysarum polysaccharides (HPS) on the Wnt/
β
-catenin signal pathway in db/db mice with diabetic nephropathy.
Method
2
Fifty db/db mice were randomly divided into model group, irbesartan group, and high, middle, and low-dose HPS experimental groups according to their body mass, with 10 mice in each group, and another 10 C57BL/6 mice were selected as a normal group. The normal group and the model group were given 5 mL·kg
-1
·d
-1
distilled water, the irbesartan group was given 22.75 mg·kg
-1
·d
-1
irbesartan suspension, and the high, middle, and low-dose HPS experimental groups were given 200, 100, and 50 mg·kg
-1
·d
-1
HPS suspensions, respectively. The mice in the 6 groups were given intragastric administration once a day for 12 weeks. The general state, blood glucose (GLU), 24 h urine protein (UTP), blood creatinine (SCr), and urea nitrogen (BUN) of mice in each group were determined. The pathological changes in the kidney tissue were observed by hematoxylin-eosin staining (HE). The protein and mRNA expression levels of Wnt1,
β
-catenin, glycogen synthesis kinase-3
β
(GSK-3
β
), and phosphorylated GSK-3
β
(p-GSK-3
β
) in the kidney were detected by Western blot and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR).
Result
2
After treatment for 12 weeks, as compared with the normal group, the general state of mice in the model group was worse and the pathological ultrastructural lesions of kidney tissues were obvious. The levels of GLU, 24 h UTP, SCr, and BUN in the model group increased (
P
<
0.01). As compared with the model group, the general state and renal pathological ultrastructure of mice in the high and middle-dose HPS groups were improved to some extent, and the levels of SCr, BUN, and 24 h UTP in the high and middle-dose HPS groups decreased (
P
<
0.05,
P
<
0.01). As compared with the normal group, the expression levels of Wnt1,
β
-catenin, GSK-3
β
, and p-GSK-3
β
protein and mRNA in the model group were higher (
P
<
0.01), while the expression levels of Wnt1,
β
-catenin, GSK-3
β
, and p-GSK-3
β
protein and mRNA in the high and middle-dose HPS groups were lower than those in the model group (
P
<
0.05,
P
<
0.01).
Conclusion
2
HPS can alleviate the renal injury of diabetic nephropathy to some extent, and its mechanism may be related to the inhibition of the activation of the Wnt/
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