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学科主题: 临床医学
题名:
Hydrogen sulfide regulates vascular endoplasmic reticulum stress in apolipoprotein E knockout mice
作者: Chen Zhi-fang5; Zhao Bin5; Tang Xiu-ying4; Li Wei1; Zhu Lu-lu1; Tang Chao-shu2,3; Du Jun-bao1; Jin Hong-fang1
关键词: hydrogen sulfide ; atherosclerosis ; endoplasmic reticulum stress
刊名: CHINESE MEDICAL JOURNAL
发表日期: 2011-11-05
DOI: 10.3760/cma.j.issn.0366-6999.2011.21.005
卷: 124, 期:21, 页:3460-3467
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Medicine, General & Internal
研究领域[WOS]: General & Internal Medicine
关键词[WOS]: UNFOLDED PROTEIN RESPONSE ; SMOOTH-MUSCLE-CELLS ; E-DEFICIENT MICE ; NITRIC-OXIDE ; CARBON-MONOXIDE ; ATHEROSCLEROSIS ; APOPTOSIS ; DISEASE ; PROGRESSION ; CASPASE-12
英文摘要:

Background Atherosclerosis is an important cardiovascular disease, becoming a major and increasing health problem in developed countries. However, the possible underlying mechanisms were not completely clear. In 2009, our research group first discovered that hydrogen sulfide (H(2)S) as a novel gastrotransmitter played an important anti-atherosclerotic role. The study was designed to examine the regulatory effect of hydrogen sulfide (H(2)S) on endoplasmic reticulum stress (ERS) in apolipoprotein E knockout (apoE(-/-)) mice fed a Western type diet.

Methods C57BL/6 mice and homozygous apoE(-/-) mice were fed a Western type diet. C57BL/6 mice were injected intraperitoneally with normal saline (5 ml/kg per day) as control group. The apoE(-/-) mice were treated with the same dose of normal saline as the apoE(-/-) group, injected intraperitoneally with sodium hydrosulfide (NaHS, an H(2)S donor, 56 mu mol/kg per day) as the apoE(-/-)+NaHS group and injected intraperitoneally with DL-propargylglycine (PPG, a cystathionine-gamma-lyase inhibitor, 50 mg/kg, per day) as the apoE(-/-) +PPG group. After 10 weeks, the mice were sacrificed and the plasma lipids were detected. Sections of aortic root from these animals were examined for atherosclerotic lesions by HE and oil red 0 staining. The aortic ultrastructure and microstructure were analyzed with the help of light and electronic microscope. Glucose-regulated protein 78 (GRP78), caspase-12, copper-andzinc-containing superoxide dismutase (Cu/ZnSOD) and Mn-containing superoxide dismutase (MnSOD) protein expression in aortic tissues were detected with immunohistochemistry. The level of intracellular reactive oxygen species (ROS) were measured by using a commercial assay kit.

Results Compared with control mice, apoE(-/-) mice showed increased plasma levels of total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL), decreased high density lipoprotein (HDL), increased aortic plaque size, destroyed ultra-structure of aortic tissue, and increased expression of GRP78 and caspase-12 proteins. Compared with apoE(-/-) mice, H(2)S donor-treated apoE(-/-) mice showed a decreased plasma LDL level, lessened plaque necrosis and attenuated aortic ultra-structural disorder. H(2)S donor-treatment induced GRP78 expression but suppressed caspase-12 expression in aortic lesions. However, compared with apoE(-/-) mice, PPG treated apoE(-/-) mice showed enlarged plaque size, more severe ultrastructural disorder of the aortic tissue and reduced GRP78 staining in aortic lesions. The plasma lipids and the staining of caspase-12 in apoE(-/-) + PPG rats did not significantly differ from those in the apoE(-/-)-mice. Consistently, H(2)S induced SOD expression, accompanied by a reduced level of ROS.

Conclusion H(2)S plays a regulatory role in aortic ERS and reduces atherosclerotic lesions in apoE(-/-) mice fed with a Western type diet. Chin Med J 2011;124(21):3460-3467

语种: 英语
所属项目编号: 2011CB503904 ; 2012CB517806 ; 81070212 ; 30821001 ; 30801251
项目资助者: Major Basic Research Development Program of China ; National Natural Science Foundation of China
WOS记录号: WOS:000297658200006
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/63677
Appears in Collections:北京大学第一临床医学院_儿科_期刊论文

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作者单位: 1.Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing 100191, Peoples R China
2.Peking Univ, Dept Pediat, Hosp 1, Beijing 100034, Peoples R China
3.Peking Univ, Dept Physiol & Pathophysiol, Hlth Sci Ctr, Beijing 100034, Peoples R China
4.Peking Univ, Dept Electron Microscope, Hosp 1, Beijing 100034, Peoples R China
5.Beijing Jishuitan Hosp, Dept Emergency Med, Beijing 100035, Peoples R China

Recommended Citation:
Chen Zhi-fang,Zhao Bin,Tang Xiu-ying,et al. Hydrogen sulfide regulates vascular endoplasmic reticulum stress in apolipoprotein E knockout mice[J]. CHINESE MEDICAL JOURNAL,2011,124(21):3460-3467.
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