联麦氧钒对糖尿病大鼠内质网应激介导心肌细胞凋亡的抑制作用及其机制

doi:10.13481/j.1671-587x.20150317

Abstract

Abstract:

Objective To investigate the inhibitroy effect of bis(maltolato)oxovanadium(Ⅳ) (BMOV) on endoplasmic reticulum stress(ERS)-induced apoptosis of cardiomyocytes of the rats with diabetes mellitus (DM) and possible mechanisms, and to provide a theoretical basis for the clinical study on diabetic cardiomyopathy(DCM). Methods 35 male Wistar rats were selected, among them 10 rats were randomly selected and used as control group, and they were admistrated intraperitoneally with citric acid buffer (55 mg·kg^-1) and normal drinking water for 4 weeks.The remaining 25 rats were admistrated intraperitoneally with streptozotocin (STZ).1 week later, the rats with the level of fasting blood glucose greater than or equal to 13.3 mmol·L^-1 were used as DM models. Finally 20 DM rats were randomly divided into DM group and BMOV group (n=10).The rats in DM group were administered with normal drinking water for 3 weeks.The rats in BMOV group were administered with BMOV in drinking water for 3 weeks.The myocardium tissue was taken for TUNEL staining to observe the apoptosis;Western blotting method was used to detect the levels of glucose-regulated protein 78 (GRP78), CCCAAT/enhancer binding homologous protein (CHOP), X-box binding protein 1(XBP-1);qPCR was used to dectect the XBP-1 mRNA expression levels in myocardium tissue of the rats in various groups. Results The TUNEL staining Results showed that the apoptotic cells in cyocardium tissue of the rats in control group were few, in control group the apoptotic index(AI) was 0.80 + 0.63;compared with control group, the apoptosis of myocardial cells in DM group was significantly increased, and the AI was increased (P<0.05);compared with DM group, the apoptosis of myocardial cells in BMOV group was significantly decreased, and the AI was decreased (P<0.05).The Western blotting Results showed that the expression levels of GRP78, CHOP.and XBP-1 of the rats in DM group were significantly higher than those in control group(P<0.05);and the expression levels of GRP78, CHOP and XBP-1 of the rats in BMOV group were lower than those in DM group(P<0.05).The qPCR Results showed that the XBP-1 mRNA expression level of the rats in DM group was higher than that in control group(P<0.05), and the XBP-1 mRNA expression level of the rats in BMOV group was lower than that in DM group(P<0.05). Conclusion BMOV has protective effects on the myocardial cells of the DM rats, and its mechanism may be related to inhibition of ERS and apoptosis of myocardial cells induced by ERS.

Key words: bis(maltolato)oxovanadium(Ⅳ), diabetic cardiomyopathy, endoplasmic reticulum stress, X-box binding protein 1

CLC Number:

R587.2

LI Ying, CONG Xiaoqiang, ZHAO Liangchen, XIE Lin, LIU Ya. Inhibitory effect of BMOV on endoplasmic reticulum stress-induced cardiomyocyte apoptosis of diabetic rats and its mechanism[J].Journal of Jilin University Medicine Edition, 2015, 41(03): 522-526.

References

[1] Yang W, Lu J, Weng J, et al. Prevalence of diabetes among men and women in China [J].New Engl J Med, 2010, 362(12):1090-1101.

[2] Roglic G, Unwin N.Mortality attributable to diabetes: estimates for the year 2010[J].Diabetes Res Clin Pract, 2010, 87(1):15-19.

[3] Cai L, Li W, Wang G, et al.Hyperglycemia-induced apoptosis in mouse myocardium: mitochondrial cytochrome C-mediated caspase-3 activation pathway[J].Diabetes, 2002, 51(6):1938-1948.

[4] 王秋利, 孔俭, 李杰, 等.联麦氧钒对糖尿病大鼠晶体超微结构的影响[J].中华医学杂志, 2000, 80(4):77-78.

[5] 孙捷, 丁怡敏, 邵明柏, 等.联麦氧钒对自发性高血压大鼠心肌结构的影响[J].吉林大学学报:医学版, 2005, 31(3):398-400.

[6] Pawson EJ, Duran-Jimenez B, Surosky R, et al.Engineered zinc finger protein-mediated VEGF-a activation restores deficient VEGF-a in sensory neurons in experimental diabetes[J].Diabetes, 2010, 59(2):509-518.

[7] Wasan KM, Risovic V, Yuen VG, et al.Effects of three and eight weeks oral administration of bis(maltolato)oxovanadium(IV) on plasma homocysteine and cysteine levels in streptozotocin-induced diabetic rats[J].Exp Clin Cardiol, 2004, 9(2):125-129.

[8] 韦金儒, 张雅莉.3-硝基酪氨酸与糖尿病心肌病大鼠心肌细胞凋亡的关系研究[J].中国病理生理杂志, 2011, 27(2):243-248.

[9] 王时俊, 邹云增, 孙爱军, 等.氧化应激在乙醛引起的心肌细胞凋亡中的作用[J].中国病理生理杂志, 2008, 24(8):1464-1468.

[10] Chen J, Zhang Z, Cai L.Diabetic cardiomyopathy and its prevention by nrf2: current status[J].Diabetes Metab J, 2014, 38(5):337-345.

[11] Bugger H, Abel ED.Molecular mechanisms of diabetic cardiomyopathy[J].Diabetologia, 2014, 57(4):660-671.

[12] Sozen E, Karademir B, Ozer NK.Basic mechanisms in endoplasmic reticulum stress and relation to cardiovascular diseases[J].Free Radic Biol Med, 2014, 78(1):30-41.

[13] Liu Y, Adachi M, Zhao S, et al.Preventing oxidative stress: a new role for XBP1[J]. Cell Death Different, 2009, 16(6):847-857.

[14] Huang CC, Li Y, Lopez AB, et al.Temporal regulation of Cat-1 (cationic amino acid transporter-1) gene transcription during endoplasmic reticulum stress[J].Biochem J, 2010, 429(1):215-224.

[15] Ozturk N, Olgar Y, Ozdemir S.Trace elements in diabetic cardiomyopathy: An electrophysiological overview[J].World J Diabetes, 2013, 4(4):92-100.

[16] Clark TA, Deniset JF, Heyliger CE, et al.Alternative therapies for diabetes and its cardiac complications: role of vanadium[J].Heart Fail Rev, 2014, 19(1):123-132.

[17] 田慧.糖尿病:女性心血管病变重要危险因素[J].中国实用内科杂志, 2014, 34(1):18-21.

[18] 金茜, 李小凤.糖尿病患者认知功能减退相关危险因素研究进展[J].中国实用内科杂志, 2013, 33(3):243-245.

Inhibitory effect of BMOV on endoplasmic reticulum stress-induced cardiomyocyte apoptosis of diabetic rats and its mechanism

PDF (PC)

Like

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 10

Metrics

Comments

Recommended 0

[1]	PAN Hong, WANG Yufeng, HUANG Haipeng, ZHANG Liying, ZHONG Zhen, MA Shiqi, DONG Li, WANG Hongfeng. Influence of Adjust Zang Dredge Meridian electroacupuncture in expression of GRP78 in sciatic nerve cells of rats with diabetic peripheral neuropathy and its neuroprotective effect [J]. Journal of Jilin University(Medicine Edition), 2018, 44(06): 1124-1130.
[2]	GONG Qing, SONG Qiuying, QIU Lijing, HUANG Xiaowei, ZHAO Wenhai. Recovery effect of PLGA microsphere-loaded VAP combined with BMMSCs on sciatic nerve injury of rats and its mechanism [J]. Journal of Jilin University(Medicine Edition), 2018, 44(06): 1174-1178.
[3]	YU Lei, TANG Geng, FANG Fang, LI Xin, GONG Shouliang, WANG Zhicheng, WANG Jianfeng. Expressions of IRE1α and XBP1 mRNA and proteins in mouse testis cells induced by low dose ionizing radiation [J]. Journal of Jilin University(Medicine Edition), 2018, 44(05): 919-923.
[4]	XIAO Bin, LIU Rongrong, LIU Bingtong, ZHANG Xuewu. Induction effect of TTF1-NP on human hepatoma cell apoptosis through ERS-mediated pathway [J]. Journal of Jilin University Medicine Edition, 2015, 41(06): 1118-1123.
[5]	YU Yang, XU Ye, LIU Shibing, YI Dan, LI Songyan, WANG Xiaojun. Introduction effect of hydrogen peroxide on autophagy and apoptosis in Hela cells through endoplasmic reticulum stresssignal pathway [J]. Journal of Jilin University Medicine Edition, 2015, 41(03): 437-441.
[6]	ZOU Yong-guo,ZHOU Chun-yan,PIAO Mei-hua,LIU Nan,YUE Yun,FENG Chun-sheng. Influence of isoflurane in apoptosis and endoplasmic reticulum stress of PC12 cells induced by Aβ25-35 of rats and its mechanism [J]. Journal of Jilin University Medicine Edition, 2014, 40(02): 224-228.
[7]	ZHEN Yong-zhan,JI Chun-mei,ZHAO Yu-fang,YAN Feng,LIU Xue-jun,WANG Mei-mei,XU Ai-jun. Apoptosis-induction of lidamycin in human multiple  myeloma SKO-007 cells enhanced by bortezomid through endoplasmic reticulum stress pathway [J]. Journal of Jilin University Medicine Edition, 2013, 39(6): 1206-1210.
[8]	GU Cheng, JIA Yu-jie\|MIN Lian-qiu. Protective effect of rosiglitazone on focal cerebral ischemia injury in type 2 diabetic rats and its mechanism  [J]. J4, 2012, 38(3): 451-455.
[9]	SUN Jing-Chun, WANG Chun-Yan, XU Hui, LI An-Sheng. Effect of endoplasmic reticulum stress in renal injury of fluorosis rats [J]. J4, 2009, 35(6): 992-995.
[10]	XI Shu-gang，ZHANG Xue-xin， ZHANG Wen-jie，WEI Zheng-ren，ZHAO Chun-yan. Protective effect of total arasolides of aralia elata(Miq) seem on cardiomyopathy in rats with early stage diabetes and its mechanism [J]. J4, 2008, 34(2): 209-213.