內質網應激反應在嚴重燒傷大鼠心肌細胞凋亡中的作用_《中國修復重建外科雜志》

作者：

褚萬立 , 柴家科 , 馮永強 , 馬麗 , 胡超

解放軍總醫院第一附屬醫院燒傷整形科（北京，100048）;

關鍵詞：

內質網應激反應心肌細胞凋亡燒傷大鼠

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目的內質網應激反應（endoplasmic reticulum stress，ERS）介導的凋亡是真核細胞重要凋亡途徑之一，
通過觀察嚴重燒傷大鼠心肌ERS 不同通路蛋白表達變化，探討其在心肌細胞凋亡中的可能作用。方法雄性7 周齡
Wistar 大鼠64 只，體重200 ～ 220 g；隨機分為兩組，每組32 只。實驗組大鼠背部制備30% 體表面積Ⅲ度燙傷；對照組
制備假傷模型。傷后1、4、7、14 d 兩組各處死8 只大鼠取心肌組織，透射電鏡觀察心肌超微結構變化，TUNEL 法檢測心
肌細胞凋亡，Western blot 檢測ERS 相關蛋白，如葡萄糖調節蛋白78（glucose regulated protein 78，GRP 78）、C/EBP 同源
蛋白（C/EBP-homologous protein，CHOP）、半胱氨酸天冬氨酸蛋白酶12（Caspase 12）剪切體表達變化。結果大鼠均
存活至實驗結束。透射電鏡觀察示實驗組大鼠心肌細胞呈凋亡改變。傷后各時間點實驗組心肌細胞凋亡指數均明顯高
于對照組（P lt; 0.05），傷后1、4、7 d 凋亡指數逐漸升高，14 d 時下降，各時間點間比較差異均有統計學意義（P lt; 0.05）。實
驗組心肌細胞GRP78、CHOP 及Caspase 12 剪切體蛋白表達持續升高，其中各時間點GRP 78 及Caspase 12 剪切體表達
均較對照組顯著升高，差異有統計學意義（P lt; 0.05）；除傷后1 d 外，其余各時間點實驗組CHOP 蛋白表達均較對照組升
高（P lt; 0.05）。結論嚴重燒傷后大鼠心肌發生ERS，其中CHOP、Caspase 12 介導的凋亡通路活化，ERS 可能是心肌
細胞凋亡的途徑之一。

引用本文： 褚萬立,柴家科,馮永強,馬麗,胡超. 內質網應激反應在嚴重燒傷大鼠心肌細胞凋亡中的作用. 中國修復重建外科雜志, 2012, 26(5): 592-596. doi: 復制

1.	c-independent activation of caspase-9 by caspase-12. J Biol Chem, 2002, 277(37): 34287-34294.
2.	Carlson DL, Horton JW. Cardiac molecular signaling after burn trauma. J Burn Care Res, 2006, 27(5): 669-675.
3.	Rasheva VI, Domingos PM. Cellular responses to endoplasmic reticulum stress and apoptosis. Apoptosis, 2009, 14(8): 996-1007.
4.	Rao RV, Ellerby HM, Bredesen DE. Coupling endoplasmic reticulum stress to the cell death program. Cell Death Differ, 2004, 11(4): 372-380.
5.	蔡建華, 柴家科, 申傳安, 等. 燒傷、沖擊傷及燒沖復合傷后大鼠早期血清中性粒細胞彈性蛋白酶的變化及意義. 中華醫學雜志, 2010, 90(24): 1707-1710.
6.	Zhang JP, Ying X, Liang WY, et al. Apoptosis in cardiac myocytes during the early stage after severe burn. J Trauma, 2008, 65(2): 401-408.
7.	張西聯, 黃躍生, 黨永明, 等. 生脈注射液對大鼠燒傷后心肌細胞凋亡的影響. 第三軍醫大學學報, 2007, 29(2): 94-96.
8.	萬義福, 許寶華, 張玉珍, 等. 大鼠嚴重燒傷后心肌細胞GRP94表達變化及其意義. 中國比較醫學雜志, 2008, 18(2): 43-47.
9.	柴家科, 盛志勇. 進一步重視大面積深度燒傷皮膚替代物的研究. 中華燒傷雜志, 2002, 18(2): 73-74.
10.	Williams FN, Herndon DN, Suman OE, et al. Changes in cardiac physiology after severe burn injury. J Burn Care Res, 2011, 32(2): 269-274.
11.	George I, Sabbah HN, Xu K, et al. β-adrenergic receptor blockade reduces endoplasmic reticulum stress and normalizes calcium handling in a coronary embolization model of heart failure in canines. Cardiovasc Res, 2011, 91(3): 447-455.
12.	Tao J, Zhu W, Li Y, et al. Apelin-13 protects the heart against ischemia-reperfusion injury through inhibition of ER-dependent apoptotic pathways in a time-dependent fashion. Am J Physiol Heart Circ Physiol, 2011, 301(4): H1471-1486.
13.	Xin W, Li X, Lu X, et al. Involvement of endoplasmic reticulum stress-associated apoptosis in a heart failure model induced by chronic myocardial ischemia. Int J Mol Med, 2011, 27(4): 503-509.
14.	Sari FR, Widyantoro B, Thandavarayan RA, et al. Attenuation of CHOP-mediated myocardial apoptosis in pressure-overloaded dominant negative p38α mitogen-activated protein kinase mice. Cell Physiol Biochem, 2011, 27(5): 487-496.
15.	Yin XL, Zhang W, Yang Y, et al. Increasing expression of (CCAAT enhancer binding protein) homologous protein induced by endoplasmic reticulum stress in myocardium after cardiac arrest and resuscitation in rat. Resuscitation, 2012, 83(3): 378-385.
16.	Chen S, Du J, Liang Y, et al. Sulfur dioxide inhibits excessively activated endoplasmic reticulum stress in rats with myocardial injury. Heart Vessels, 2011. [Epub ahead of print].
17.	Minamino T, Komuro I, Kitakaze M. Endoplasmic reticulum stress as a therapeutic target in cardiovascular disease. Circ Res, 2010, 107(9): 1071-1082.
18.	Zang Q, Maass DL, White J, et al. Cardiac mitochondrial damage and loss of ROS defense after burn injury: the beneficial effects of antioxidant therapy. J Appl Physiol, 2007, 102(1): 103-112.
19.	Groenendyk J, Sreenivasaiah PK, Kim do H, et al. Biology of endoplasmic reticulum stress in the heart. Circ Res, 2010, 107(10): 1185-1197.
20.	Wu T, Dong Z, Geng J, et al. Valsartan protects against ER stress-induced myocardial apoptosis via CHOP/Puma signaling pathway in streptozotocin-induced diabetic rats. Eur J Pharm Sci, 2011, 42(5): 496-502.
21.	Ballard-Croft C, Carlson D, Maass DL, et al. Burn trauma alters calcium transporter protein expression in the heart. J Appl Physiol, 2004, 97(4): 1470-1476.
22.	Morishima N, Nakanishi K, Takenouchi H, et al. An endoplasmic reticulum stress-specific caspase cascade in apoptosis. Cytochrome.

1. c-independent activation of caspase-9 by caspase-12. J Biol Chem, 2002, 277(37): 34287-34294.
2. Carlson DL, Horton JW. Cardiac molecular signaling after burn trauma. J Burn Care Res, 2006, 27(5): 669-675.
3. Rasheva VI, Domingos PM. Cellular responses to endoplasmic reticulum stress and apoptosis. Apoptosis, 2009, 14(8): 996-1007.
4. Rao RV, Ellerby HM, Bredesen DE. Coupling endoplasmic reticulum stress to the cell death program. Cell Death Differ, 2004, 11(4): 372-380.
5. 蔡建華, 柴家科, 申傳安, 等. 燒傷、沖擊傷及燒沖復合傷后大鼠早期血清中性粒細胞彈性蛋白酶的變化及意義. 中華醫學雜志, 2010, 90(24): 1707-1710.
6. Zhang JP, Ying X, Liang WY, et al. Apoptosis in cardiac myocytes during the early stage after severe burn. J Trauma, 2008, 65(2): 401-408.
7. 張西聯, 黃躍生, 黨永明, 等. 生脈注射液對大鼠燒傷后心肌細胞凋亡的影響. 第三軍醫大學學報, 2007, 29(2): 94-96.
8. 萬義福, 許寶華, 張玉珍, 等. 大鼠嚴重燒傷后心肌細胞GRP94表達變化及其意義. 中國比較醫學雜志, 2008, 18(2): 43-47.
9. 柴家科, 盛志勇. 進一步重視大面積深度燒傷皮膚替代物的研究. 中華燒傷雜志, 2002, 18(2): 73-74.
10. Williams FN, Herndon DN, Suman OE, et al. Changes in cardiac physiology after severe burn injury. J Burn Care Res, 2011, 32(2): 269-274.
11. George I, Sabbah HN, Xu K, et al. β-adrenergic receptor blockade reduces endoplasmic reticulum stress and normalizes calcium handling in a coronary embolization model of heart failure in canines. Cardiovasc Res, 2011, 91(3): 447-455.
12. Tao J, Zhu W, Li Y, et al. Apelin-13 protects the heart against ischemia-reperfusion injury through inhibition of ER-dependent apoptotic pathways in a time-dependent fashion. Am J Physiol Heart Circ Physiol, 2011, 301(4): H1471-1486.
13. Xin W, Li X, Lu X, et al. Involvement of endoplasmic reticulum stress-associated apoptosis in a heart failure model induced by chronic myocardial ischemia. Int J Mol Med, 2011, 27(4): 503-509.
14. Sari FR, Widyantoro B, Thandavarayan RA, et al. Attenuation of CHOP-mediated myocardial apoptosis in pressure-overloaded dominant negative p38α mitogen-activated protein kinase mice. Cell Physiol Biochem, 2011, 27(5): 487-496.
15. Yin XL, Zhang W, Yang Y, et al. Increasing expression of (CCAAT enhancer binding protein) homologous protein induced by endoplasmic reticulum stress in myocardium after cardiac arrest and resuscitation in rat. Resuscitation, 2012, 83(3): 378-385.
16. Chen S, Du J, Liang Y, et al. Sulfur dioxide inhibits excessively activated endoplasmic reticulum stress in rats with myocardial injury. Heart Vessels, 2011. [Epub ahead of print].
17. Minamino T, Komuro I, Kitakaze M. Endoplasmic reticulum stress as a therapeutic target in cardiovascular disease. Circ Res, 2010, 107(9): 1071-1082.
18. Zang Q, Maass DL, White J, et al. Cardiac mitochondrial damage and loss of ROS defense after burn injury: the beneficial effects of antioxidant therapy. J Appl Physiol, 2007, 102(1): 103-112.
19. Groenendyk J, Sreenivasaiah PK, Kim do H, et al. Biology of endoplasmic reticulum stress in the heart. Circ Res, 2010, 107(10): 1185-1197.
20. Wu T, Dong Z, Geng J, et al. Valsartan protects against ER stress-induced myocardial apoptosis via CHOP/Puma signaling pathway in streptozotocin-induced diabetic rats. Eur J Pharm Sci, 2011, 42(5): 496-502.
21. Ballard-Croft C, Carlson D, Maass DL, et al. Burn trauma alters calcium transporter protein expression in the heart. J Appl Physiol, 2004, 97(4): 1470-1476.
22. Morishima N, Nakanishi K, Takenouchi H, et al. An endoplasmic reticulum stress-specific caspase cascade in apoptosis. Cytochrome.

《中國修復重建外科雜志》

內質網應激反應在嚴重燒傷大鼠心肌細胞凋亡中的作用

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《中國修復重建外科雜志》

內質網應激反應在嚴重燒傷大鼠心肌細胞凋亡中的作用

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

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