中医药研究论丛

27-2.1 中药复方对DN 小鼠肾组织TGF-β1、PTEN 蛋白表达的影响

TJ TCM.27(2) : 1-23, 2024 1DOI : 10.6516/TJTCM.202409_27(2).0001

中药复方对DN小鼠肾组织TGF-β1、PTEN蛋白表达的影响

Effects of Traditional Chinese Medicine Compound on the Expression of TGF-β1 and PTEN Proteins in Tissues of DN Mice

黄景宏1 李政育2,*

1士林锦禾中医诊所,台北,台湾

2育生中医诊所,台北,台湾

【摘要】

目的:本研究目的在探讨中药复方加味建瓴汤与加味金匮肾气丸对糖尿病肾病的疗效和作用机制。材料与方法:本研究采用实验研究,将雄性小鼠45只分为五组,一组为正常对照组,另外四组分别为diabetic control(以下简称为DC组)作为糖尿病对照组;Chinese medicine 1(以下简称为CM1组)为加味建瓴汤治疗组;Chinese medicine 2(以下简称为CM2组)为加味金匮肾气丸治疗组;angiotensin-converting enzyme inhibitors(以下简称为ACEI组)为西药captopril治疗组。在诱导糖尿病小鼠模型前後分别测量小鼠的体重、血糖。成功诱导糖尿病小鼠模型後的第4周加测尿总蛋白、肌酐等生化数值。在牺牲小鼠後,测量其肾重,计算肾脏肥大指数并肾脏组织切片做免疫组织化学染色。

结果:和DC组小鼠相比,CM2组对於小鼠的血糖值的影响不显着,但可以明显减少尿总蛋白排泄量以及尿总蛋白/肌酐比值(urinary protein/creatinine ratio, UPCR),亦可以改善小鼠的肾脏肥大指数。CM1组治疗可以降低小鼠的血糖值、减少尿总蛋白排泄量以及改善肾脏肥大指数,但在尿总蛋白/肌酐比值则没有显着差异。肾脏重量和肾脏肥大指数上,中药两组间及与ACEI组间无明显差异。相较於DC组,CM1组、CM2组及ACEI组肾组织TGF-β1蛋白表达下降,uPA蛋白表达增强,但在肾组织IL-6蛋白表达及PTEN蛋白表达,各组之间则没有显着差异。

结论:加味建瓴汤、加味金匮肾气丸和西药captopril三组药物,都可以改善糖尿病肾病小鼠之尿总蛋白排泄量和肾脏肥大指数,其机转是通过降低肾组织TGF-β1表达、增强uPA信号转导通路达成。

【关键词】坏死性筋膜炎、中医药

Huang Chin-Hung1

Lee Chen-Yu2,*

1Shilin Jinhe Traditional Chinese Medicine Clinic, Taipei, Taiwan

2Yu Sheng Traditional Chinese Medicine Clinic, Taipei, Taiwan

【Summary】

Purpose: The study aims to clarify the traditional Chinese medicine composed of modified prescription of Jian Ling Decoction and modified prescription of Jin Gui Shen Qi Wan for the improvement and molecular mechanisms of diabetic nephropathy.Material and method: This research was conducted in laboratory. The 45, male, 5 weeks old, mice were fed for 3 weeks. 8 weeks old mice were used and randomly divided into 5 groups with group 1 as normal control group consisted of 9 mice. Other groups were designed to produce mouse models of diabetes. Each group consisted of 9 mice after successful modeling. Group 2 was DC group, as diabetic control group, did not reviewed any treatment. CM1 group, as traditional Chinese medicine experimental group 1, were given modified prescription of Jian Ling Decoction. CM2 group, as traditional Chinese medicine experimental group 2, were given modified prescription of Jin Gui Shen Qi Wan. ACEI group, as Western medicine control group, were given captopril.The body weight and blood glucose of the mice were measured at week 0, the second week and the fourth week after modeled. In addition, experiment was designed to evaluate the effect of TCM on urinary total protein, creatinine and other biochemical indexes of STZ-induced diabetic mice at fourth week after modeled.

Results: The effect of modified prescription of Jin Gui Shen Qi wan on blood sugar is not significant by comparing with untreated diabetic control mice. But the urinary total protein excretion and the urinary total protein / creatinine ratio (UPCR) were significantly reduced in CM2 group. Besides, the renal hypertrophy index of mice had been improved as well. These results were similar to the results of ACEI group.

The modified prescription of JianLing Decoction could lower blood glucose levels, reduce urinary total protein excretion, and improve renal hypertrophy index in mice, but there is no significant difference in urinary total protein / creatinine ratio. There was no significant difference between the CM1 group, CM2 group and ACEI group for the renal weight and renal hypertrophy index.Compared with DC group, CM1 group, CM2 group and ACEI group could reduce the expression of TGF-β1 protein and increase the expression of uPA protein, but there was no significant difference in IL-6 protein and PTEN protein between all groups.

Conclusion: All of three treatment groups including the modified prescription of JianLing Decoction, the modified prescription of Jin Gui Shen Qi wan and captopril could significantly improve urinary total protein excretion and renal hypertrophy index and relieved renal pathological damage in STZ-induced diabetic mice. The mechanism was related to the decrease of TGF-β1 and uPA protein in renal tissue, but not related to the expression of IL-6 and PTEN protein in renal tissue.

【Keywords】

Diabetic nephropathy, STZ-induced diabetic models in mice, Jin Gui Shen Qi wan, Jian Ling Decoction; TGF-β1; PTEN