
浏览全部资源
扫码关注微信
1.北京中医药大学 中医学院,北京 100029;
2.首都医科大学 附属复兴医院,北京 100038
孙文,助理研究员,从事中医养生理论和技术开发研究,E-mail:sunweng00897@163.com
吴丽丽,助理研究员,从事中医药防治糖尿病临床和基础研究,E-mail:qingniao_566@163.com
收稿日期:2019-01-21,
网络出版日期:2019-03-04,
纸质出版日期:2019-11-20
移动端阅览
孙文, 许光远, 侯丹, 等. 糖耐康对自发性2型糖尿病小鼠NE,
Wen SUN, Guang-yuan XU, Dan HOU, et al. Effect of Tangnaikang on Imbalance Between NE and α1-AT in Spontaneous Type 2 Diabetic Mouse[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(22): 22-27.
孙文, 许光远, 侯丹, 等. 糖耐康对自发性2型糖尿病小鼠NE,
Wen SUN, Guang-yuan XU, Dan HOU, et al. Effect of Tangnaikang on Imbalance Between NE and α1-AT in Spontaneous Type 2 Diabetic Mouse[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(22): 22-27. DOI: 10.13422/j.cnki.syfjx.20191221.
目的:
2
观察中药糖耐康(Tangnaikang,TNK)对2型糖尿病(T2DM)的ob/ob小鼠中性粒细胞弹性蛋白酶(NE),
α
1
-抗胰蛋白酶(
α
1
-AT)蛋白表达的调节作用。
方法:
2
将32只雄性SPF级ob/ob小鼠按体质量随机分为模型组(生理盐水),TNK高剂量组(TNK溶液16.04 g·kg
-1
),TNK中剂量组(TNK溶液8.02 g·kg
-1
)和TNK低剂量组(TNK溶液4.01 g·kg
-1
)。另取8只C57BL/6J小鼠作为正常组(生理盐水)。灌胃4周。每周记录小鼠一般状态和体质量和空腹血糖(FBG),第25天进行口服葡萄糖耐量(OGTT)实验,第27天进行胰岛素耐量(ITT)实验,灌胃结束后,取血清检测空腹胰岛素(Fins),NE,
α
1
-AT,取脂肪组织检测NE,
α
1
-AT,p-IRS1,葡萄糖转运蛋白4(GLUT4)蛋白表达水平。
结果:
2
与正常组比较,模型组ob/ob小鼠体质量显著增大,糖脂代谢指标均呈糖尿病表现,血清和脂肪组织NE显著增加(
P
<
0.01),
α
1
-AT显著减少(
P
<
0.01)。与模型组比较,TNK高剂量组体质量,甘油三酯(TG),总胆固醇(TC),低密度脂蛋白(LDL)指标均显著减少(
P
<
0.01),高密度脂蛋白(HDL)显著增加(
P
<
0.01),FBG,Fins,胰岛素抵抗指数(HOMA-IR),曲线下面积(AUC)
ogtt
,AUC
ITT
均显著减少(
P
<
0.01),血清和脂肪组织NE显著减少(
P
<
0.01),
α
1
-AT显著增加(
P
<
0.01),脂肪组织p-IRS1和GLUT4明显增加(
P
<
0.05)。
结论:
2
TNK能够降低ob/ob小鼠体质量,改善糖脂代谢,升高
α
1
-AT水平,降低NE水平,调节IRS1/GLUT4信号的关键位点,可能是其改善中性粒细胞介导的脂肪组织IR的作用机制之一。
Objective:
2
To observe the regulatory effect of Tangnaikang (TNK) on imbalance between neutrophil elastase (NE) and
α
1
-antitrypsin (
α
1
-AT) in ob/ob mice with type 2 diabetes mellitus (T2DM).
Method:
2
Thirty-two male SPF ob/ob mice were randomly divided into model group (DM
normal saline) and high-dose TNK group (TNKH
TNK solution 16.04 g·kg
-1
)
middle-dose TNK group (TNKM
TNK solution 8.02 g·kg
-1
) and low-dose TNK group (TNKL
TNK solution 4.01 g·kg
-1
). Another 8 C57BL/6J mice were included in normal group (Con
saline). The experiment lasted for four weeks. The general state
body weight (BW) and fasting blood glucose (FBG) of the mice were recorded weekly
the oral glucose tolerance (OGTT) test was performed on the 25
th
day
the insulin tolerance (ITT) test was performed on the 27
th
day
and the area under the curve (AUC) was calculated. After the end of the experiment
serum was used to detect the level of fasting insulin (Fins)
insulin resistance index (HOMA-IR)
total triglyceride (TG)
total cholesterol (TC)
high-density lipoprotein (HDL)
low-density lipoprotein (LDL)
NE and
α
1
-AT. Adipose tissue was used to detect the expressions of NE
α
1
-AT
phosphor-insulin receptor substrate 1 antibody (p-IRS1) and glucose transporter 4 (GLUT4) proteins.
Result:
2
Compared with the Con group
the BW of the ob/ob mice of the model group increased significantly
the glucose and lipid metabolism indexes showed diabetes
the serum and adipose tissue NE increased significantly (
P
<
0.01)
and the
α
1
-AT decreased significantly (
P
<
0.01). Compared with the DM group
the BW
TG
TC
and LDL indexes in the TNKH group were significantly decreased (
P
<
0.01)
the HDL was significantly increased (
P
<
0.01)
and the FBG
Fins
HOMA-IR
AUC
ogtt
and AUC
ITT
were significantly decreased (
P
<
0.01)
serum and adipose tissue NE decreased significantly (
P
<
0.01)
α
1
-AT increased significantly (
P
<
0.01)
and adipose tissue p-IRS1 and GLUT4 increased significantly (
P
<
0.05).
Conclusion:
2
TNK can reduce the BW of ob/ob mice
improve glycolipid metabolism
increase
α
1
-AT level
decrease NE level
and regulate IRS1-GLUT4 signaling pathway
which may be one of its mechanisms in improving IR of adipose tissue mediated by neutrophil.
Ogurtsova K , Da R F J , HUANG Y , et al . IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040 [J]. Diabetes Res Clin Pract , 2017 , 128 : 40 - 50 .
Hotamisligil G S . Inflammation, metaflammation and immunometabolic disorders [J]. Nature , 2017 , 542 ( 7640 ): 177 - 185 .
Saltiel A R , Olefsky J M . Inflammatory mechanisms linking obesity and metabolic disease [J]. J Clin Invest , 2017 , 127 ( 1 ): 1 - 4 .
Kolaczkowska E , Kubes P . Neutrophil recruitment and function in health and inflammation [J]. Nat Rev Immunol , 2013 , 13 ( 3 ): 159 - 175 .
Mansuy-Aubert V , ZHOU Q L , XIE X , et al . Imbalance between neutrophil elastase and its inhibitor alpha1-antitrypsin in obesity alters insulin sensitivity, inflammation, and energy expenditure [J]. Cell Metab , 2013 , 17 ( 4 ): 534 - 548 .
牛洁 , 刘铜华 , 王志程 , 等 . 糖耐康颗粒对胰岛素抵抗3T3-L1脂肪细胞炎症因子的影响 [J]. 深圳中西医结合杂志 , 2009 , 19 ( 2 ): 65-68,76 .
郭翔宇 , 段颖 , 李娟娥 , 等 . 糖耐康对肥胖Zucker大鼠血糖的影响及其机制(英文) [J]. 中西医结合学报 , 2010 , 8 ( 6 ): 535 - 540 .
LIU T , WANG F , LI Y , et al . Regulation of the insulin resistance pathways in 3T3-L1 adipocytes by Tangnaikang (a herbal formula)-medicated serum [J]. Planta Med , 2008 , 74 ( 9 ): A282 .
王芬 , 何华亮 , 江南 , 等 . 糖耐康对自发性2型糖尿病KKAy小鼠胰岛素信号转导的影响 [J]. 中国实验方剂学杂志 , 2008 , 14 ( 1 ): 46 - 49 .
黄继汉 , 黄晓晖 , 陈志扬 , 等 . 药理试验中动物间和动物与人体间的等效剂量换算 [J]. 中国临床药理学与治疗学 , 2004 , 9 ( 9 ): 1069 - 1072 .
李鹏程 , 朴春红 , 张岚 , 等 . 荞麦壳黄酮提取物对2型糖尿病大鼠的血糖改善作用及机制 [J]. 食品科学 , 2017 , 38 ( 5 ): 244 - 250 .
WANG L , GAO P , ZHANG M , et al . Prevalence and ethnic pattern of diabetes and prediabetes in China in 2013 [J]. JAMA , 2017 , 317 ( 24 ): 2515 - 2523 .
HU C , JIA W . Diabetes in China: epidemiology and genetic risk factors and their clinical utility in personalized medication [J]. Diabetes , 2018 , 67 ( 1 ): 3 - 11 .
Donath M Y , Shoelson S E . Type 2 diabetes as an inflammatory disease [J]. Nat Rev Immunol , 2011 , 11 ( 2 ): 98 - 107 .
候丹 , 刘铜华 . 橄榄苦苷对糖尿病小鼠肝脏糖代谢的作用及机制 [J]. 中国实验方剂学杂志 , 2018 , 24 ( 23 ): 134 - 139 .
黄链莎 , 刘铜华 , 孙文 , 等 . 桑叶黄酮对糖尿病大鼠血糖水平的影响及机制探讨 [J]. 中国实验方剂学杂志 , 2018 , 24 ( 16 ): 152 - 156 .
Kolaczkowska E , Kubes P . Neutrophil recruitment and function in health and inflammation [J]. Nat Rev Immunol , 2013 , 13 ( 3 ): 159 - 175 .
Talukdar S , Oh D Y , Bandyopadhyay G , et al . Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase [J]. Nat Med , 2012 , 18 ( 9 ): 1407 - 1412 .
Pham C T . Neutrophil serine proteases: specific regulators of inflammation [J]. Nat Rev Immunol , 2006 , 6 ( 7 ): 541 - 550 .
Ingalls A M , Dickie M M , Snell G D . Obese, a new mutation in the house mouse [J]. J Hered , 1950 , 41 ( 12 ): 317 - 318 .
Mansuy-Aubert V , ZHOU Q L , XIE X , et al . Imbalance between neutrophil elastase and its inhibitor alpha1-antitrypsin in obesity alters insulin sensitivity, inflammation, and energy expenditure [J]. Cell Metab , 2013 , 17 ( 4 ): 534 - 548 .
0
浏览量
13
下载量
1
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621