
浏览全部资源
扫码关注微信
1.天津中医药大学 研究生院,天津 301617
2.天津医科大学 朱宪彝纪念医院,天津 300134
尚鑫,在读硕士,从事中西医结合治疗糖尿病及其并发症研究,E-mail:690379010@qq.com
常柏,主任医师,博士生导师,从事中西医结合治疗糖尿病及其并发症研究,E-mail:changbai1972@126.com
收稿日期:2020-12-23,
网络出版日期:2021-03-05,
纸质出版日期:2021-05-05
移动端阅览
尚鑫,任晓霞,陈栋等.抵挡汤对糖尿病心肌病小鼠NLRP3炎症小体的作用及机制[J].中国实验方剂学杂志,2021,27(09):19-25.
SHANG Xin,REN Xiao-xia,CHEN Dong,et al.Effect and Mechanism of Didangtang on NLRP3 Inflammasomes in Diabetic Cardiomyopathy Mice[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(09):19-25.
尚鑫,任晓霞,陈栋等.抵挡汤对糖尿病心肌病小鼠NLRP3炎症小体的作用及机制[J].中国实验方剂学杂志,2021,27(09):19-25. DOI: 10.13422/j.cnki.syfjx.20210603.
SHANG Xin,REN Xiao-xia,CHEN Dong,et al.Effect and Mechanism of Didangtang on NLRP3 Inflammasomes in Diabetic Cardiomyopathy Mice[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(09):19-25. DOI: 10.13422/j.cnki.syfjx.20210603.
目的
2
探讨不同剂量抵挡汤对糖尿病小鼠心肌炎性病变的影响。
方法
2
选取60只C57BL/6J小鼠,随机分为正常组(10只)和模型组(50只)。模型组小鼠采用高脂饲料联合链脲佐菌素(STZ)腹腔注射制备糖尿病小鼠模型,模型制备成功后继续高脂饲料喂养,8周后采用超声成像平台检测小鼠心功能,出现心功能减退,则糖尿病心肌病小鼠造模成功,剔除未成模小鼠,最终成模小鼠40只,模型组小鼠按照心功能随机分为模型组、抵挡汤低、中、高(1.5,3,6 g·kg
-1
)和辛伐他汀组(0.001 5 g·kg
-1
),每组8只。超声成像平台检测小鼠心功能,全自动生化仪检测小鼠空腹血糖(FBG),甘油三酯(TG),总胆固醇(TC),苏木素-伊红(HE)染色观察心肌组织病理学改变,蛋白免疫印迹法(Western blot)检测心肌组织NOD样受体3(NLRP3),硫氧还蛋白相互作用蛋白(TXNIP),半胱氨酸的天冬氨酸蛋白水解酶-1(Caspase-1),白细胞介素-1
β
(IL-1
β
)蛋白水平,检测心肌组织活性氧(ROS)含量。
结果
2
与正常组比较,模型组的FBG,TC,TG的水平显著升高(
P
<
0.01),左室射血分数(EF),左室短轴缩短率(FS)数值显著降低(
P
<
0.01),ROS表达明显升高(
P
<
0.05),心肌组织中NLRP3,TXNIP,Caspase-1,IL-1
β
表达明显升高(
P
<
0.05)。与模型组比较,抵挡汤中、高剂量组及辛伐他汀组FBG,TC,TG水平明显降低(
P
<
0.05);抵挡汤各剂量组及辛伐他汀组EF,FS均有改善(
P
<
0.05),抵挡汤中剂量组变化更为明显(
P
<
0.05);HE染色结果发现,抵挡汤能够改善小鼠心肌组织病理学变化;抵挡汤各剂量组及辛伐他汀组小鼠ROS表达水平明显减少,抵挡汤中剂量组变化更为明显;抵挡汤各剂量组NLRP3,TXNIP,Caspase-1,IL-1
β
表达明显降低,抵挡汤中剂量降低心肌组织NLRP3,TXNIP,Caspase-1表达的效果更为明显;抵挡汤高剂量降低心肌组织IL-1
β
表达的效果更为明显。
结论
2
抵挡汤可通过抑制NLRP3炎症小体的激活,改善糖尿病心肌病小鼠心肌炎性病变。
Objective
2
To investigate the effects of different doses of Didangtang on myocardial inflammatory lesions in diabetic mice.
Method
2
Sixty C57BL/6J mice were randomly divided into normal group (
n
=10) and model group (
n
=50). The diabetic mice in the model group were established by intraperitoneal injection of high-fat diet combined with streptozotocin (STZ). After model reproducing, the mice were fed with high-fat diet. After 8 weeks, the cardiac function of the mice was detected by using an ultrasound imaging platform. If the cardiac function decreased, the diabetic cardiomyopathy mice were modeled successfully. The nonmodel mice were eliminated, and finally 40 model mice were modeled. The rats in the model group were randomly divided into model group, low, medium and high dose of Didangtang group(1.5,3,6 g·kg
-1
) and simvastatin group(0.001 5 g·kg
-1
) according to heart function, with 8 rats in each group. The cardiac function of mice was detected by ultrasound imaging platform, fiber bragg grating(FBG), triglyceride(TG) and total cholesterol(TC) were detected by automatic biochemical analyzer, hematoxylin-eosin (HE) staining was used to observe the pathological changes of myocardium, and the levels of NOD-like receptor3(NLRP3), thiomdoxin interaction protein(TXNIP), cysteinyl aspartate specific proteinase-1(Caspase-1) and Interleukin-1
β
(IL-1
β
) in myocardial tissue, as well as the content of reactive oxygen species(ROS) were detected by Western blot.
Result
2
Compared with the normal control group, the levels of FBG, TC and TG in the model group significantly increased (
P
<
0.01); the values of EF and FS significantly decreased (
P
<
0.01); the expression of ROS significantly increased (
P
<
0.05), and the expressions of NLRP3, TXNIP, Caspase-1 and IL-1
β
in the myocardial tissue significantly increased (
P
<
0.05). Compared with the model group, the levels of FBG, TC and TG in the middle and high dose groups of Didangtang and simvastatin groups significantly decreased (
P
<
0.05); the EF and FS in each dose group and simvastatin group improved (
P
<
0.05), and the change in the middle dose group was more obvious (
P
<
0.05). HE staining showed that Didangtang could improve the pathological changes of myocardial tissue in mice, the ROS expression levels of mice in each dose group of Didangtang and simvastatin group significantly reduced, especially in the middle dose group, the expression levels of NLRP3, TXNIP, Caspase-1 and IL-1
β
in each dose group significantly decreased, and the effect of middle dose of Didangtang on reducing expressions of NLRP3, TXNIP and Caspase-1 in myocardial tissue was more obvious, the effect of high dose of Didangtang on reducing the expression of IL-1
β
in myocardial tissue was more obvious.
Conclusion
2
Didangtang can improve myocardial inflammatory lesions in diabetic cardiomyopathy mice by inhibiting the activation of NLRP3 inflammasome.
项伟玲 , 金丽琴 , 高峰 , 等 . 黑苦荞茎叶对2型糖尿病小鼠的治疗作用及其对其胰腺、脾脏的影响 [J]. 中国应用生理学杂志 , 2019 , 35 ( 2 ): 140 - 144 .
FALCAO-PIRES I , LEITE-MOREIRA A F . Diabetic cardiomyopathy:understanding the molecular and cellular basis to progress in diagnosis and treatment [J]. Heart Fail Rev , 2012 , 17 ( 3 ): 325 - 440 .
张静 , 李刚 . 糖尿病心肌病病理机制研究 [J]. 医学信息 , 2020 , 33 ( 2 ): 43 - 46 .
位晨晨 , 钟明 . 糖尿病心肌病的发病机制 [J]. 心血管病学进展 , 2020 , 41 ( 2 ): 135 - 139 .
陈纪烨 , 马度芳 , 王永成 , 等 . 免疫炎症反应在心力衰竭心肌纤维化中的研究进展 [J]. 中国免疫学杂志 , 2020 , 36 ( 20 ): 2534 - 2539 .
LIBERALE L , CARBONE F , CAMICI G G , et al . IL-1 β and statin treatment in patients with myocardial infarction and diabetic cardiomyopathy [J]. J Clin Med , 2019 , 8 ( 11 ): 1764 .
常柏 , 李巧芬 , 李春深 , 等 . 抵挡汤早期干预对2型糖尿病大鼠血清IL-4、IL-13水平及主动脉TNF-αmRNA表达的影响 [J]. 四川中医 , 2013 , 31 ( 3 ): 48 - 50 .
朱超 , 朱莹莹 . Ⅱ型糖尿病动物模型的构建 [J]. 中国实验动物学报 , 2013 , 21 ( 2 ): 84 - 88 .
徐慧琳 , 徐郭珺 , 姚君 , 等 . 阿魏酸对糖尿病小鼠心肌病变的影响及其机制 [J]. 中国应用生理学杂志 , 2018 , 34 ( 3 ): 238 - 241 .
童敏 , 李文东 , 肖皓亮 , 等 . 糖元阳片对链脲佐菌素诱导糖尿病小鼠保护作用的研究 [J]. 湖南中医杂志 , 2017 , 33 ( 9 ): 163 - 165 .
EGUCHI K , NAGAI R . Islet inflammation in type 2 diabetes and physiology [J]. J Clin Invest , 2017 , 127 ( 1 ): 14 - 23 .
郭振 , 樊迪 , 唐其柱 . 活性氧在糖尿病心肌病中的作用机制研究进展 [J]. 解放军医学杂志 , 2020 , 45 ( 12 ): 1294 - 1298 .
TU J L , CHEN W P , CHENG Z J , et al . EGb761 ameliorates cell necroptosis by attenuating RIP1-mediated mitochondrial dysfunction and ROS production in both in vivo and in vitro models of Alzheimer's disease [J]. Brain Res , 2020 , 1736 : 146730 .
WILSON A J , GILL E K , ABUDALO R A , et al . Reactive oxygen species signalling in the diabetic heart:emerging prospect for therapeutic targeting [J]. Heart , 2018 , 104 ( 4 ): 293 - 299 .
ZHOU R , TARDIVEL A , THORENS B , et al . Thioredoxin-interacting protein links oxidative stress to inflammasome activation [J]. Nat Immunol , 2010 , 11 : 136 - 140 .
LIU D L , ZENG X , LI X , et al . Advances in the molecular mechanisms of NLRP3 inflammasome activators and inactivators [J]. Biochem Pharmacol , 2020 , doi: 10.1016/j.bcp.2020.113863 http://dx.doi.org/10.1016/j.bcp.2020.113863 .
何梦含 . 从TXNIP介导NLRP3炎症小体激活途径研究三七总皂苷减轻衰老大鼠神经炎症反应的作用机制 [D]. 宜昌 : 三峡大学 , 2019 .
叶婷 , 阿克拜尔·乌普 , 岳薇薇 , 等 . 异搏定通过抑制TXNIP介导的细胞凋亡和炎症减轻高脂喂养小鼠的糖尿病前期神经病变 [J]. 医学研究杂志 , 2020 , 49 ( 4 ): 113 - 117 .
崔勇和 , 沈先敏 . 白藜芦醇抑制TXNIP/NLRP3信号通路改善脂多糖诱导的肾小管上皮细胞炎性损伤 [J]. 天津中医药 , 2019 , 36 ( 5 ): 495 - 498 .
0
浏览量
19
下载量
6
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621