[1]杨 芳,高素文,刘 旋,等.丹参酮ⅡA通过调控p38MAPK/NF-κB信号通路减轻糖尿病雄性大鼠生殖损伤实验研究[J].陕西医学杂志,2024,(5):610-615.[doi:DOI:10.3969/j.issn.1000-7377.2024.05.007]
　YANG Fang,GAO Suwen,LIU Xuan,et al.Tanshinone ⅡA alleviates reproductive damage in diabetic male rats by regulating p38MAPK/NF-κB signaling pathway[J].,2024,(5):610-615.[doi:DOI:10.3969/j.issn.1000-7377.2024.05.007]
点击复制

丹参酮ⅡA通过调控p38MAPK/NF-κB信号通路减轻糖尿病雄性大鼠生殖损伤实验研究
分享到：

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
期数:
2024年5期
页码:
610-615
栏目:
基础研究
出版日期:
2024-05-05

文章信息/Info

Title:
Tanshinone ⅡA alleviates reproductive damage in diabetic male rats by regulating p38MAPK/NF-κB signaling pathway
作者:
杨 芳1; 高素文1; 刘 旋1; 韦志坤2; 郑聪聪1
(1.邯郸市中心医院,河北 邯郸 056002; 2.邯郸市第一医院,河北 邯郸 056002)
Author(s):
YANG Fang; GAO Suwen; LIU Xuan; WEI Zhikun; ZHENG Congcong
(Handan Central Hospital,Handan 056002,China)
关键词:
糖尿病;  生殖损伤;  丹参酮ⅡA;  p38丝裂原活化蛋白激酶/核因子-κB信号通路;  氧化应激;  炎症反应;  大鼠
Keywords:
Diabetes mellitus;  Reproductive damage;  Tanshinone ⅡA;  p38MAPK/NF-κB signaling pathway;  Oxidative stress;  Inflammatory response;  Rats
分类号:
R -33
DOI:
DOI:10.3969/j.issn.1000-7377.2024.05.007
文献标志码:
A
摘要:
目的:探讨丹参酮ⅡA(TanⅡA)对糖尿病雄性大鼠生殖损伤的影响及其机制。方法:随机选取43只雄性SD大鼠中的35只通过高糖高脂喂养联合腹腔注射链脲佐菌素构建糖尿病动物模型,并分为模型组、TanⅡA(6 mg/kg)组、SB203580[p38丝裂原活化蛋白激酶(p38MAPK)抑制剂,2 mg/kg]组和TanⅡA+SB203580(6 mg/kg+2 mg/kg)组,每组8只; 剩余8只设为正常组。给药治疗4周后,检测空腹血糖(FBG)水平。ELISA法检测血清睾酮(T)、黄体生成素(LH)、卵泡刺激素(FSH)含量。检测精子质量(浓度、存活率和活力),测量睾丸重量并计算睾丸指数。HE染色法观察睾丸组织病理学改变。检测睾丸组织总超氧化物歧化酶(T-SOD)、过氧化氢酶(CAT)活力和丙二醛(MDA)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、IL-8含量。Western blot法检测睾丸组织p38MAPK、p-p38MAPK、核因子-κB p65(NF-κB p65)、p-NF-κB p65、高迁移率族蛋白B1(HMGB1)表达。结果:与模型组比较,TanⅡA组、SB203580组和TanⅡA+SB203580组FBG水平比较差异无统计学意义(均P>0.05); T、LH、FSH含量和精子浓度、存活率及活力升高(均P<0.05); 睾丸重量和睾丸指数升高(均P<0.05); 睾丸组织病理学改变明显改善; T-SOD、CAT活力升高且MDA、TNF-α、IL-1β、IL-8含量降低(均P<0.05); HMGB1水平和p-p38MAPK/p38MAPK、p-NF-κB p65/NF-κB p65比值降低(均P<0.05)。TanⅡA+SB203580组以上指标优于TanⅡA组和SB203580组(均P<0.05)。结论:TanⅡA可能通过抑制p38MAPK/NF-κB信号通路,降低氧化应激水平和炎症反应,从而减轻糖尿病雄性大鼠生殖损伤。
Abstract:
Objective:To investigate the effect of tanshinone ⅡA(TanⅡA)on reproductive damage in diabetic male rats and its mechanism.Methods:Randomly selected thirty-five out of fourty-three SD male rats were used to prepare the diabetic animal model by feeding with high glucose and fat combined with intraperitoneal injection of streptozotocin,and which were divided into the model group,TanⅡA(6 mg/kg)group,SB203580(p38 mitogen activated protein kinase [p38MAPK] inhibitor,2 mg/kg)group and TanⅡA+SB203580(6 mg/kg+2 mg/kg)group,with eight rats in each group.And another eight rats were set as normal group.After four weeks of medication,the level of fasting blood glucose(FBG)was detected.ELISA method was used to detect the content of serum testosterone(T),luteinizing hormone(LH)and follicle-stimulating hormone(FSH).The sperm quality(sperm concentration,survival rate and vitality)was analyzed.The quality of testis was weighed and calculating testicular index.HE staining was used to observe the pathological changes of testis tissue.The activity of total superoxide dismutase(T-SOD),catalase(CAT)and the content of malondialdehyde(MDA),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),IL-8 in testicular tissue were determined.Western blot method was used to detect the expression of p38MAPK,p-p38MAPK,nuclear factor-κB p65(NF-κB p65),p-NF-κB p65,high mobility group protein B1(HMGB1).Results: Compared with the model group,there was no significant difference in FBG level of TanⅡA,SB203580 and TanⅡA+SB203580 groups(all P>0.05).The content of T,LH,FSH and the sperm concentration,survival rate,vitality were increased(all P<0.05).The testis mass and testis index were increased(all P<0.05).The pathological changes of testis tissue were improved.The activity of T-SOD,CAT and the content of MDA,TNF-α,IL-1β,IL-8 were decreased(all P<0.05).The ratio of p-p38MAPK/p38MAPK,p-NF-κB p65/NF-κB p65 and the expression of HMGB1 were decreased(all P<0.05).The effects of TanⅡA+SB203580 on the indexes were better than those of TanⅡA group and SB203580 group(all P<0.05).Conclusion:TanⅡA may reduce reproductive damage in male diabetic rats by inhibiting p38MAPK/NF-κB signaling pathway,reducing oxidative stress and inflammatory response.

参考文献/References:

[1] 朱怡睿,张莹.糖尿病对生殖功能的影响[J].医学综述,2021,27(4):771-777.
[2] 夏雨果,陈秋,高坪,等.三才连梅颗粒通过Nrf2/HO-1信号通路对糖尿病小鼠生精功能的影响[J].陕西中医,2023,44(4):421-426,432.
[3] 杨芳,马静芬,郑聪聪,等.苦参素对2型糖尿病雄性大鼠生殖损伤及Nrf2/HO-1信号通路的影响[J].天津中医药,2023,40(9):1175-1182.
[4] RAKHSHANDEH H,RAJABI-KHASEVAN H,SAVIANO A,et al.Protective effect of portulaca oleracea on streptozotocin-induced type Ⅰ diabetes-associated reproductive system dysfunction and inflammation[J].Molecules,2022,27(18):6075-6084.
[5] SUDIRMAN S,SU C Y,TSOU D,et al.Hippocampus kuda protein hydrolysate improves male reproductive dysfunction in diabetic rats [J].Biomed Pharmacother,2021,140(8):111760.
[6] KONG Z L,SUDIRMAN S,HSU Y C,et al.Fucoxanthin-rich brown algae extract improves male reproductive function on streptozotocin-nicotinamide-induced diabetic rat model[J].Int J Mol Sci,2019,20(18):4485-4497.
[7] 刘宝枚,王金玉,王明芳,等.地黄合剂介导p38 MAPK通路对糖尿病大鼠主动脉的影响[J].西北药学杂志,2023,38(1):101-106.
[8] 吕朝阳,杨营军,敖文,等.高良姜素抑制IRAK-1/MAPK/NF-κB信号通路对糖尿病大鼠心肌损伤的影响[J].天津中医药,2022,39(11):1476-1482.
[9] 陈红,李春花,王文军,等.α1-抗胰蛋白酶联合骨髓间充质干细胞通过p38 MAPK/NF-κB信号通路调节糖尿病大鼠视网膜病变的研究[J].海南医学院学报,2021,27(1):11-17.
[10] 张海云,韩伟东,刘海梅,等.丹参酮ⅡA对急性肺损伤小鼠炎症因子和氧化应激水平的影响[J].解剖学研究,2020,42(6):491-495.
[11] 丁维,钟立仁,张海波,等.丹参酮ⅡA磺酸钠对高脂血症勃起功能障碍大鼠 Nrf2/HO-1通路及勃起功能的影响[J].陕西中医,2020,41(11):1520-1523,1538.
[12] ZHOU H,ZHAO Y,PENG W,et al.Effect of sodium tanshinone ⅡA sulfonate injection on blood lipid in patients with coronary heart disease:A systematic review and meta-analysis of randomized clinical trials[J].Front Cardiovasc Med,2021,8(11):770746.
[13] 付鑫,卢杰,李潞,等.丹参酮ⅡA对Apoe基因敲除动脉粥样硬化小鼠主动脉TNF-α/p38MAPK/NF-κB/RBP4信号通路变化研究[J].辽宁中医药大学学报,2018,20(1):18-21.
[14] 万强,杨玉萍,刘中勇.丹参酮ⅡA通过抑制p38MAPK通路减轻PM2.5对血管内皮细胞的损伤[J].中国病理生理杂志,2016,32(4):597-601.
[15] 陆包伟,刘露梅,王能,等.龟鹿二仙胶对糖尿病大鼠生殖损伤的保护作用及机制[J].中国实验方剂学杂志,2022,28(19):1-8.
[16] 曾存良,张鑫鹏,胥雄飞,等.黄连素对糖尿病大鼠血管钙化的影响及其机制研究[J].现代中西医结合杂志,2019,28(8):799-805,849.
[17] OZTIN H,CAGILTAY E,CAGLAYAN S,et al.Kisspeptin levels in idiopathic hypogonadotropic hypogonadism diagnosed male patients and its relation with glucose-insulin dynamic[J].Gynecol Endocrinol,2016,32(12):991-994.
[18] 乔光华,焦建伟,张永灿.丹参酮ⅡA对自然衰老大鼠睾丸生殖细胞的损害机制[J].热带医学杂志,2019,19(6):715-718,810.
[19] 魏书瑶,冯珊珊,马菲菲,等.氧化应激在2型糖尿病发生发展中的作用机制[J].西北国防医学杂志,2021,42(6):557-562.
[20] 黎珊珊,区岛良,张梅,等.紫草素对糖尿病周围神经病变大鼠的治疗作用及对腺苷酸活化蛋白激酶/核因子E2相关因子2信号通路的影响[J].陕西医学杂志,2023,52(6):683-687.
[21] 李萍,王静,戴成祥,等.移植前输注间充质干细胞对脑死亡供鼠移植肾炎症细胞浸润及TNF-α和IL-1β表达的影响[J].成都医学院学报,2020,15(1):40-45.
[22] ZHOU M,XU W,WANG J,et al.Boosting mTOR-dependent autophagy via upstream TLR4-MyD88-MAPK signaling and downstream NF-κB pathway quenches intestinal inflammation and oxidative stress injury[J].EBioMedicine,2018,35(9):345-360.
[23] 朱志杰,王选康,左晓霜,等.光生物调节通过抑制氧化应激和继发炎症促进脊髓损伤修复[J].空军军医大学学报,2022,43(4):287-293.
[24] 冷凤,史玲,刘丽莉.针刺调控p38MAPK/NF-κB信号通路对脑卒中后抑郁症大鼠干预机制[J].陕西中医,2022,43(3):292-295,333.
[25] GALLUCCI G M,ALSUWAYT B,AUCLAIR A M,et al.Fenofibrate downregulates NF-κB signaling to inhibit pro-inflammatory cytokine secretion in human THP-1 macrophages and during primary biliary cholangitis[J].Inflammation,2022,45(6):2570-2581.
[26] 吴文婷,李敏,蒲文娟.白藜芦醇对慢性阻塞性肺疾病大鼠 p38丝裂原活化蛋白激酶/核因子-κB信号通路的影响[J].陕西医学杂志,2023,52(11):1489-1492,1534.
[27] 段建兴,刘文军,曾跃勤,等.肝脏p38MAPK/NF-κB通路在大鼠烧伤休克期切痂以减轻炎症反应中的作用[J].感染、炎症、修复,2020,21(1):16-21.
[28] 黄丹,胡韬韬,陈丹.血清高迁移率族蛋白B1与糖尿病肾病病人肾功能、炎症因子及氧化应激指标的相关性研究[J].蚌埠医学院学报,2022,47(8):1021-1025.

相似文献/References:

[1]段继源,王光哲,曹艳,等.胰岛素强化治疗对急性冠脉综合征合并糖尿病患者PCI术后血小板功能的影响[J].陕西医学杂志,2016,(10):1411.
[2]叶睿,任力杰.2型糖尿病患者下肢动脉病变发生率及危险因素分析[J].陕西医学杂志,2016,(10):1426.
[3]庄晖,李利波,梁梅珍,等.妊娠期糖尿病孕妇胎儿脐动脉频谱血流收缩期最大血流速度与舒张期血流速度比值对胎儿宫内窘迫的预测价值[J].陕西医学杂志,2017,(06):715.
[4]严玲玲,苏建彬 △,王雪琴.胰岛α细胞功能与2型糖尿病肾脏病变相关性研究[J].陕西医学杂志,2018,(12):1576.
[5]齐婷,左红,黎国红,等.不同剂量阿托伐他汀钙片联合阿司匹林肠溶片对糖尿病患者动脉粥样硬化斑块稳定性影响的对比分析*[J].陕西医学杂志,2019,(1):92.
　QI Ting,ZUO Hong,LI Guohong,et al.Comparative analysis of the effects of different doses of atorvastatin tablets combined withaspirin entericcoated tablets on the stability of diabetic atherosclerotic plaque[J].,2019,(5):92.
[6]汤克虎,高峻峰,任尽平.药物涂层球囊在糖尿病患者冠状动脉小血管病变治疗中的应用研究*[J].陕西医学杂志,2019,(4):432.
[7]周 祎,张 宁,刘晓荣,等.结核感染T淋巴细胞实验和Xpert MTB/RIF检测在糖尿病并发菌阴性肺结核患者诊断中的价值*[J].陕西医学杂志,2019,(7):885.
　ZHOU Yi,ZHANG Ning,LIU Xiaorong,et al.Diagnostic efficiency of T-SPOT.TB and Gen-Xpert MTB/RIF in detecting smear-negative pulmonary tuberculosis combined with diabetes mellitus.[J].,2019,(5):885.
[8]陈辅萍.慢性阻塞性肺疾病并发感染性肺炎危险因素分析[J].陕西医学杂志,2020,49(1):102.
[9]王 晶,刘易婷,刘 哲.替米沙坦联合瑞舒伐他汀治疗糖尿病合并冠心病对患者外周胰岛素抵抗、糖化血红蛋白、脂蛋白和心肌缺血的影响[J].陕西医学杂志,2022,51(5):595.[doi:DOI:10.3969/j.issn.1000-7377.2022.05.019]
　WANG Jing,LIU Yiting,LIU Zhe.Effects of telmisartan combined with rosuvastatin on peripheral insulin resistance,glycosylated hemoglobin,lipoproteins and myocardial ischemia in diabetic patients with coronary heart disease[J].,2022,51(5):595.[doi:DOI:10.3969/j.issn.1000-7377.2022.05.019]
[10]韦文合.达格列净联合唑来膦酸治疗老年糖尿病合并骨质疏松症疗效及对患者骨代谢、骨密度水平的影响[J].陕西医学杂志,2023,52(11):1574.[doi:DOI:10.3969/j.issn.1000-7377.2023.11.027]
　WEI Wenhe.Efficacy of dapagliflozin combined with zoledronic acid in treatment of elderly diabetic patients with osteoporosis and its effect on bone metabolism and bone mineral density[J].,2023,52(5):1574.[doi:DOI:10.3969/j.issn.1000-7377.2023.11.027]

备注/Memo

备注/Memo:
基金项目:河北省医学科学研究课题(20210509)
更新日期/Last Update: 2024-05-06