The role of carbonic anhydrase III and autophagy in type 2 diabetes with cardio-cerebrovascular disease.
The role of carbonic anhydrase III and autophagy in type 2 diabetes with cardio-cerebrovascular disease.
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碳酸酐酶Ⅲ和自噬在2型糖尿病合并心脑血管疾病中的作用
DOI：
10.1007/s11011-021-00839-9
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发表时间：
2021-12
影响因子：
3.6
通讯作者：
Zhou HG
中科院分区：
文献类型：
--
作者：
Zhang XM;Tao YH;Zhou XL;Shang XL;Gong XB;Liu YC;Huang YY;Chen G;Yu ZY;Wang JT;Du ZG;Wu GF;Zhang Y;Guo JC;Zhou HG
2型糖尿病（T2DM）是老年人最常见的慢性疾病之一。T2DM可增加心脑血管疾病（CCD）的发生风险，其主要病理变化为动脉粥样硬化（AS）。同时，碳酸酐酶（CAs）参与了AS斑块的形成和发展。然而，碳酸酐酶III （carbononic anhydrase III， CAIII）的确切生理机制尚不清楚，CAIII蛋白与T2DM合并CCD的相关性研究也未见。8周龄的糖尿病小鼠（db/db - / -小鼠）和野生型小鼠（wt小鼠）正常饲养至32周龄，采用生物力学方法检测颈动脉血管开口角；用超微结构观察大鼠大脑皮层和心肌的变化，用电镜观察自噬的变化；苏木精、伊红（HE）染色观察组织结构、炎症及细胞损伤情况；TUNEL染色观察细胞凋亡情况；免疫组化、Western Blot检测caii、IL-17、p53蛋白表达水平，Western Blot检测Beclin-1、LC3、NF-κB蛋白表达水平。所有统计分析均使用PRISM软件进行。与wt小鼠相比，db/db−/−小鼠颈动脉开放角度明显增大。电镜结果显示db/db−/−小鼠大脑皮层和心脏组织自噬减少，胞内细胞器超微结构受损。HE染色显示，db/db−/−小鼠大脑皮层和心脏组织染色较浅，炎症细胞浸润，细胞水肿明显，心肌纤维紊乱，心肌细胞出现不同程度的变性。TUNEL染色显示，与wt小鼠相比，db/db−/−小鼠皮层和心脏组织细胞凋亡明显增加。免疫组化和Western Blot结果显示，db/db−/−小鼠皮层和心脏组织中CAIII、Beclin-1和LC3II/I的表达水平明显降低，IL-17、NF-κB和p53的表达水平明显升高。糖尿病小鼠颈动脉血管僵硬度增加，可能与AS的形成有关。自噬参与了糖尿病性CCD的发生发展。CAIII蛋白可能通过影响细胞凋亡和炎症，以某种方式参与了自噬的调节，但其机制有待进一步研究。
Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases among the elderly people. The T2DM increases the risk of cardio-cerebrovascular disease (CCD), and the main pathological change of the CCD is atherosclerosis (AS). Meanwhile, the carbonic anhydrases (CAs) are involved in the formation and progression of plaques in AS. However, the exact physiological mechanism of carbonic anhydrase III (CAIII) has not been clear yet, and there are also no correlation study between CAIII protein and T2DM with CCD. The 8-week old diabetic mice (db/db−/− mice) and wild-type mice (wt mice) were feed by a normal diet till 32 weeks, and detected the carotid artery vascular opening angle using the method of biomechanics; The changes of cerebral cortex and myocardium were watched by the ultrastructure, and the autophagy were observed by electron microscope; The tissue structure, inflammation and cell injury were observed by Hematoxylin and eosin (HE) staining; The apoptosis of cells were observed by TUNEL staining; The protein levels of CAIII, IL-17, p53 were detected by immunohistochemical and Western Blot, and the Beclin-1, LC3, NF-κB were detected by Western Blot. All statistical analysis is performed using PRISM software. Compared with wt mice, db/db−/− mice’ carotid artery open angle increased significantly. Electron microscope results indicated that autophagy in db/db−/− mice cerebral cortex and heart tissue decreased and intracellular organelle ultrastructure were damaged. HE staining indicated that, db/db−/− mice’ cerebral cortex and heart tissue stained lighter, inflammatory cells infiltration, cell edema were obvious, myocardial fibers were disorder, and myocardial cells showed different degrees of degeneration. Compared with wt mice, TUNEL staining showed that there was obviously increase in db/db−/− mice cortex and heart tissue cell apoptosis. The results of immunohistochemistry and Western Blot indicated that CAIII, Beclin-1 and LC3II/I expression levels conspicuously decreased in cortex and heart tissue of db/db−/− mice, and the expression level of IL-17, NF-κB and p53 obviously increased. The carotid artery’ vascular stiffness was increased and which was probably related with formation of AS in diabetic mice. And the autophagy participated in the occurrence and development of diabetic CCD. CAIII protein might somehow be involved in the regulation of autophagy probably through affecting cell apoptosis and inflammation, but the underlying mechanism remains to be further studied.
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影响因子：
32.4
作者：
Hubbard-Lucey, Vanessa M.;Shono, Yusuke;Maurer, Katie;West, Mallory L.;Singer, Natalie V.;Ziegler, Carly G. K.;Lezcano, Cecilia;Motta, Ana Carolina Fragoso;Schmid, Karin;Levi, Samuel M.;Murphy, George F.;Liu, Chen;Winkler, Jeffrey D.;Amaravadi, Ravi K.;Rogler, Gerhard;Dickinson, Anne M.;Holler, Ernst;van den Brink, Marcel R. M.;Cadwell, Ken
通讯作者：
Cadwell, Ken
影响因子：
2.8
作者：
Alver, Ahmet;Senturk, Ayse;Ucar, Fahri
通讯作者：
Ucar, Fahri
DOI：
10.18632/aging.100431
发表时间：
2012-02
期刊：
Aging
影响因子：
--
作者：
Cai D;Liu T
通讯作者：
Liu T
影响因子：
7.3
作者：
Kant, Shawn;Stopa, Edward G.;Silverberg, Gerald D.
通讯作者：
Silverberg, Gerald D.
影响因子：
3.3
作者：
FUNG, YC;LIU, SQ
通讯作者：
LIU, SQ