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中国全科医学 ›› 2016, Vol. 19 ›› Issue (27): 3281-3286.DOI: 10.3969/j.issn.1007-9572.2016.27.005

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c-junN端蛋白激酶1磷酸化与糖尿病大鼠早期心肌损伤关系研究

陈昕明，刘晓亮，吴伟   

  1. 110001 辽宁省沈阳市，中国医科大学附属第一医院急诊科 通信作者：吴伟，110001 辽宁省沈阳市，中国医科大学附属第一医院急诊科；E-mail：wuwei196010@126.com
  • 出版日期:2016-09-20 发布日期:2026-01-15
  • 基金资助:
    全国临床医药研究专项基金（L201257）；辽宁省科技厅科学技术计划项目（2013225049）

Relationship between c-junN Terminal Kinase 1 and Early Injury in the Myocardium of Diabetic Rats

CHEN X M,LIU X L,WU W   

  1. Department of Emergency,the First Hospital of China Medical University,Shenyang 110001,China Corresponding author:WU Wei,Department of Emergency,the First Hospital of China Medical University,Shenyang 110001,China;E-mail：wuwei196010@126.com
  • Published:2016-09-20 Online:2026-01-15

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摘要： 目的　探讨c-junN端蛋白激酶1（JNK1）磷酸化与糖尿病（DM）大鼠早期心肌损伤的关系。方法　2013年10月—2014年7月，80只SPF级雌性SD大鼠适应性喂养1周后，采用随机数字表法选取60只作为DM模型组，给予高糖高脂饮食饲养4周，一次性左下腹腹腔注射1%链脲佐菌素（STZ）溶液（35 mg/kg）；另外20只作为对照组（A组），给予普通饮食饲养4周，一次性左下腹腹腔注射等量枸橼酸缓冲液。最终共48只大鼠造模成功，采用随机数字表法分为B组、C组、D组，各16只。C组大鼠腹腔注射SP600125，D组大鼠皮下埋置含有血管紧张素Ⅱ（AngⅡ）+0.9%氯化钠溶液的植入式胶囊渗透压泵，A组、B组大鼠腹腔注射0.9%氯化钠溶液。饲养6周后，采用随机数字表法从4组大鼠中分别选取10只，检测大鼠心体比（H/B）、左心室质量指数（LVMI），HE染色观察心肌组织形态学改变，免疫组化SABC法检测JNK1、磷酸化JNK1（p-JNK1）、瞬时受体电位通道C亚族（TRPC）6、胶原蛋白Ⅰ（collagen Ⅰ）表达水平。结果　B组、C组、D组大鼠H/B大于A组，B组、D组大鼠LVMI大于A组（P<0.05）；C组大鼠H/B、LVMI小于B组、D组（P<0.05）。A组大鼠心肌细胞排列整齐，细胞间连接紧密，心肌纹理清晰；B组、C组、D组大鼠心肌细胞均有不同程度的肥大性改变，细胞间隙增宽，心肌细胞排列紊乱，心肌纹理欠清晰。B组、C组、D组大鼠JNK1、p-JNK1、TRPC6、collagen Ⅰ表达水平高于A组（P<0.05）；C组大鼠JNK1、p-JNK1、TRPC6、collagen Ⅰ表达水平低于B组（P<0.05）；D组大鼠p-JNK1、TRPC6、collagen Ⅰ表达水平高于B组、C组，JNK1表达水平高于C组（P<0.05）。结论　高糖环境可诱导JNK1磷酸化，进而影响下游TRPC6信号表达，造成胶原蛋白沉积过多，导致心肌细胞肥大和纤维化，从而引起糖尿病心肌病的发生发展。

关键词: 糖尿病, 心肌疾病, c-junN端蛋白激酶1, 瞬时受体电位通道C亚族

Abstract: Objective　To investigate the relationship between c-jun N terminal kinase 1 （JNK1） and early injury in the diabetic myocardium（DM） rats.Methods　From October 2013 to July 2014,after one-week adaptive feed of the 80 female Sprague-Dawley （SD） rats at SPF levels,60 rats were selected by random number table method.They were established as DM model group by four-week high glucose and high fat diet and a one-time left lower quadrant intraperitoneal injection of streptozotocin （STZ） at a dose of 35 mg/kg.The other 20 rats,one-time intraperitoneally injected of citrate buffer solution of same volume,were regarded as the control group （group A） with four-week normal diet.In the end,modeling of the 48 rats was established successfully.They were divided into group B,group C and group D with 16 rats in each group by random number table method.Rats in group C were given an intraperitoneal injection of SP600125,rats in group D were subcutaneously implanted with an osmotic pump to infuse angiotensin Ⅱ （Ang Ⅱ） and 0.9% sodium chlo-ride,rats in group A and group B were given an intraperitoneal injection of 0.9% sodium chlo-ride.After six-week feeding,10 rats were selected from each group through random number table method.The heart/body weight ratio （H/B） and left ventricular mass index （LVMI） were detected.The Hematoxylin and Eosin staining were used to observe the myocardial pathological changes.Immunohistochemistry SABC method was used to measure the expression level of JNK1,phosphorylation JNK1 （p-JNK1）,transient receptor potential canonical channels （TRPC） 6 and collagen Ⅰ.Results　The H/B in group B,group C and group D was higher than that in group A,and LVMI in group B and group D was higher than that in group A （P<0.05）;H/B and LVMI of rats in group C were lower than those in group B and group D （P<0.05）.The myocardial cells of rats in group A arranged in neat rows with tight junctions and clear myocardial texture;while the myocardial cells of rats in group B,group C and group D had hypertrophic changes of different degrees,characterized by dilated intercellular space,disordered cell arrangement and less clear myocardial texture.The expression level of JNK1,p-JNK1,TRPC6,and collagen Ⅰ of rats in group B,group C and group D was higher than that in group A （P<0.05）;the expression level of JNK1,p-JNK1,TRPC6,and collagen Ⅰ of rats in group C was lower that in group B （P<0.05）;the expression level of p-JNK1,TRPC6,and collagen Ⅰ of rats in group D was higher than that in group B and group C,the expression level of JNK1 in group D was higher than that in group C （P<0.05）.Conclusion　High glucose environment may induce JNK1 phosphorylation,and affect the expression of TRPC6,which will lead to an increased collagen deposition,and finally result in cardiomyocyte hypertrophy and fibrosis,and cause the occurrence and development of diabetic cardiomyopathy.

Key words: Diabetes mellitus, Cardiomyopathies, c-junN terminal kinase 1, Transient receptor potential canonical channels

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