热休克蛋白B8与糖代谢异常的相关性研究
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摘要
目的通过测定健康成人、糖耐量异常(impaired glucose tolerance, IGT)者及糖尿病(diabetes mellitus, DM)患者中小分子热休克蛋白B8(HspB8)水平,研究HspB8与糖代谢异常(abnormal glucose metabolism, AGM)的相关性。方法收集AGM者45例作为糖代谢异常组(AGM组),并根据OGTT结果将AGM组分为糖尿病组(DM组)及糖耐量异常组(IGT组)。同时随机选取同期与AGM组年龄、性别相匹配的健康者22例为对照组(N组)。分别测定各组体质量、血压、体质指数(BMI)、空腹血浆葡萄糖(GLU)、糖化血红蛋白(HbA1c)、三酰甘油(TG)、总胆固醇(CHOL)水平,用Real-time PCR方法测定各研究对象HspB8 mRNA水平的变化。结果 AGM组BMI、GLU、HbA1c、TG、CHOL均较N组高(P<0.05),AGM组HspB8 mRNA水平较N组明显降低(P<0.05);DM组HspB8 mRNA水平与IGT组及N组相比,均明显降低(P<0.05);HbA1c及血糖水平与HspB8 mRNA水平呈负相关。结论 DM组HspB8 mRNA水平明显降低,且与AGM之间存在相关性;HspB8的下降可能是导致AGM发生、发展的原因之一。
Objective To study the correlation between small heat shock protein B8(HspB8) and abnormal glucose metabolism by measuring the level of HspB8 in healthy adults, patients with impaired glucose tolerance and those with diabetes. Methods We recruited 45 patients with abnormal glucose metabolism as abnormal glucose metabolism group(AGM group) in this study. This group was divided into diabetic group(DM group) and impaired glucose tolerance group(IGT group) according to OGTT. At the same time, 22 healthy subjects of matched age and sex were randomly selected as the control group(N group). We measured the body weight, blood pressure, body mass index(BMI), and levels of fasting plasma glucose(GLU), glycosylated hemoglobin(HbA1 c), triglyceride(TG) and total cholesterol(CHOL). The changes of HspB8 transcription level were measured by Real-time PCR method. Results The levels of BMI, GLU, HbA1 c, TG and CHOL were higher in AGM group than in the control group(P<0.05). The level of HspB8 in AGM group was significantly lower than that in the control group(P<0.05). The level of HspB8 in DM group was significantly lower than that in IGT group and the control group(P<0.05). GLU and HbA1 c were negatively correlated with HspB8 transcription levels. Conclusion The transcription level of HspB8 in DM group is obviously decreased, which indicates that there is a correlation between HspB8 transcription level and diabetes. The decline of HspB8 may be one cause of the occurrence and development of abnormal glucose metabolism.
Objective To study the correlation between small heat shock protein B8(HspB8) and abnormal glucose metabolism by measuring the level of HspB8 in healthy adults, patients with impaired glucose tolerance and those with diabetes. Methods We recruited 45 patients with abnormal glucose metabolism as abnormal glucose metabolism group(AGM group) in this study. This group was divided into diabetic group(DM group) and impaired glucose tolerance group(IGT group) according to OGTT. At the same time, 22 healthy subjects of matched age and sex were randomly selected as the control group(N group). We measured the body weight, blood pressure, body mass index(BMI), and levels of fasting plasma glucose(GLU), glycosylated hemoglobin(HbA1 c), triglyceride(TG) and total cholesterol(CHOL). The changes of HspB8 transcription level were measured by Real-time PCR method. Results The levels of BMI, GLU, HbA1 c, TG and CHOL were higher in AGM group than in the control group(P<0.05). The level of HspB8 in AGM group was significantly lower than that in the control group(P<0.05). The level of HspB8 in DM group was significantly lower than that in IGT group and the control group(P<0.05). GLU and HbA1 c were negatively correlated with HspB8 transcription levels. Conclusion The transcription level of HspB8 in DM group is obviously decreased, which indicates that there is a correlation between HspB8 transcription level and diabetes. The decline of HspB8 may be one cause of the occurrence and development of abnormal glucose metabolism.
引文
[1] MASINI M, BUGLIANI M, LUPI R, et al. Autophagy in human type 2 diabetes pancreatic beta cells[J]. Diabetologia, 2009, 52(6):1083-1086.
[2] 张琼,黄晓飞,翟文海,等. 细胞自噬:糖尿病发生发展中的积极参与者[J]. 天津医药, 2015, 43(12):1470-1472.
[3] GHEMRAWI R, BATTAGLIA-HSU SF, ARNOLD C. Endoplasmic reticulum stress in metabolic disorders[J]. Cells, 2018, 7.
[4] KIM J, LIM YM, LEE MS. The role ofautophagy in systemic metabolism and human-type diabetes[J]. Mol Cells, 2018, 41:11-17.
[5] WANG Y, LI YB, YIN JJ, et al.Autophagy regulates inflammation following oxidative injury in diabetes[J]. Autophagy, 2013, 9(3):272-277.
[6] LI F, XIAO H, HU Z, et al. Exploring the multifaceted roles of heat shock protein B8 (HSPB8) in diseases[J]. Eur J Cell Biol, 2018, 97:216-229.
[7] ACUNZO J, KATSOGIANNOU M, ROCCHI P. Small heat shock proteins HSP27 (HspB1), alphaB-crystallin (HspB5) and HSP22 (HspB8) as regulators of cell death[J]. Int J Biochem Cell Biol, 2012, 44(10):1622-1631.
[8] ROELOFS MF, BOELENS WC, JOOSTEN LA, et al. Identification of small heat shock protein B8 (HSP22) as a novel TLR4 ligand and potential involvement in the pathogenesis of rheumatoid arthritis[J]. J Immunol, 2006, 176(11):7021-7027.
[9] 余玲玲,鲍慧慧,程晓曙. 热休克蛋白22在内皮损伤致动脉粥样硬化中的作用[J]. 广东医学, 2015, 36(19):3062-3064.
[10] 宁光,毕宇芳. 中国成人糖尿病流行与控制现状[C]. 营养与糖尿病并发症——达能营养中心第十六届学术会议, 武汉, 2013.
[11] 杨文英,邢小燕,林红,等. 高甘油三酯血症是非胰岛素依赖型糖尿病发病的危险因素——432例非糖尿病人群六年前瞻性观察[J]. 中华内科杂志, 1995, (9):583-586.
[12] BERENTZEN TL, JAKOBSEN MU, STEGGER JG, et al. Changes in waist circumference and the incidence of acute myocardial infarction in middle-aged men and women[J]. PLoS One, 2011, 6(10):e26849.
[13] LI XS, XU Q, FU XY, et al. Heat shock protein 22 overexpression is associated with the progression and prognosis in gastric cancer[J]. J Cancer Res Clin Oncol, 2014, 140(8):1305-1313.
[14] FUKAZAWA H, UEHARA Y. U0126 reverses Ki-ras-mediated transformation by blocking both mitogen-activated protein kinase and p70 S6 kinase pathways[J]. Cancer Res, 2000, 60(8):2104-2107.
[15] ARRIGO AP, GIBERT B. Protein interactomes of three stress inducible small heat shock proteins: HspB1, HspB5 and HspB8[J]. Int J Hyperthermia, 2013, 29(5):409-422.
[16] MORROW G, SAMSON M, MICHAUD S, et al. Overexpression of the small mitochondrial Hsp22 extends Drosophila life span and increases resistance to oxidative stress[J]. FASEB J, 2004, 18(3):598-599.
[17] MARUNOUCHI T, ABE Y, MURATA M, et al. Changes in small heat shock proteins HSPB1, HSPB5 and HSPB8 in mitochondria of the failing heart following myocardial infarction in rats[J]. Biol Pharm Bull, 2013, 36(4):529-539.
[18] POURHAMIDI K, DAHLIN LB, BOMAN K, et al. Heat shock protein 27 is associated with better nerve function and fewer signs of neuropathy[J].Diabetologia, 2011, 54(12):3143-3149.
[2] 张琼,黄晓飞,翟文海,等. 细胞自噬:糖尿病发生发展中的积极参与者[J]. 天津医药, 2015, 43(12):1470-1472.
[3] GHEMRAWI R, BATTAGLIA-HSU SF, ARNOLD C. Endoplasmic reticulum stress in metabolic disorders[J]. Cells, 2018, 7.
[4] KIM J, LIM YM, LEE MS. The role ofautophagy in systemic metabolism and human-type diabetes[J]. Mol Cells, 2018, 41:11-17.
[5] WANG Y, LI YB, YIN JJ, et al.Autophagy regulates inflammation following oxidative injury in diabetes[J]. Autophagy, 2013, 9(3):272-277.
[6] LI F, XIAO H, HU Z, et al. Exploring the multifaceted roles of heat shock protein B8 (HSPB8) in diseases[J]. Eur J Cell Biol, 2018, 97:216-229.
[7] ACUNZO J, KATSOGIANNOU M, ROCCHI P. Small heat shock proteins HSP27 (HspB1), alphaB-crystallin (HspB5) and HSP22 (HspB8) as regulators of cell death[J]. Int J Biochem Cell Biol, 2012, 44(10):1622-1631.
[8] ROELOFS MF, BOELENS WC, JOOSTEN LA, et al. Identification of small heat shock protein B8 (HSP22) as a novel TLR4 ligand and potential involvement in the pathogenesis of rheumatoid arthritis[J]. J Immunol, 2006, 176(11):7021-7027.
[9] 余玲玲,鲍慧慧,程晓曙. 热休克蛋白22在内皮损伤致动脉粥样硬化中的作用[J]. 广东医学, 2015, 36(19):3062-3064.
[10] 宁光,毕宇芳. 中国成人糖尿病流行与控制现状[C]. 营养与糖尿病并发症——达能营养中心第十六届学术会议, 武汉, 2013.
[11] 杨文英,邢小燕,林红,等. 高甘油三酯血症是非胰岛素依赖型糖尿病发病的危险因素——432例非糖尿病人群六年前瞻性观察[J]. 中华内科杂志, 1995, (9):583-586.
[12] BERENTZEN TL, JAKOBSEN MU, STEGGER JG, et al. Changes in waist circumference and the incidence of acute myocardial infarction in middle-aged men and women[J]. PLoS One, 2011, 6(10):e26849.
[13] LI XS, XU Q, FU XY, et al. Heat shock protein 22 overexpression is associated with the progression and prognosis in gastric cancer[J]. J Cancer Res Clin Oncol, 2014, 140(8):1305-1313.
[14] FUKAZAWA H, UEHARA Y. U0126 reverses Ki-ras-mediated transformation by blocking both mitogen-activated protein kinase and p70 S6 kinase pathways[J]. Cancer Res, 2000, 60(8):2104-2107.
[15] ARRIGO AP, GIBERT B. Protein interactomes of three stress inducible small heat shock proteins: HspB1, HspB5 and HspB8[J]. Int J Hyperthermia, 2013, 29(5):409-422.
[16] MORROW G, SAMSON M, MICHAUD S, et al. Overexpression of the small mitochondrial Hsp22 extends Drosophila life span and increases resistance to oxidative stress[J]. FASEB J, 2004, 18(3):598-599.
[17] MARUNOUCHI T, ABE Y, MURATA M, et al. Changes in small heat shock proteins HSPB1, HSPB5 and HSPB8 in mitochondria of the failing heart following myocardial infarction in rats[J]. Biol Pharm Bull, 2013, 36(4):529-539.
[18] POURHAMIDI K, DAHLIN LB, BOMAN K, et al. Heat shock protein 27 is associated with better nerve function and fewer signs of neuropathy[J].Diabetologia, 2011, 54(12):3143-3149.