黄连素对PCOS模型大鼠LPS /NF-κB、MAPK信号通路的影响*

doi:10.12047/j.cjap.6229.2022.029

摘要/Abstract

摘要： 目的: 探讨黄连素对多囊卵巢综合征(PCOS)模型大鼠糖脂代谢、性激素结合蛋白和脂联素(LPS)以及NF-κB、MAPK信号通路的影响。方法: 将SD雌性大鼠随机分成空白组、PCOS模型组、黄连素组(0.216 g/kg)、二甲双胍组(0.135 g/kg)和达英-35(0.18 mg/kg)组,每组10只。PCOS模型组用来曲唑(1 mg/(kg·d))连续灌胃3周,随后药物干预28 d,检测大鼠体重、卵巢和子宫指数,HE染色观察大鼠卵巢卵泡数量变化,用ELISA法检测血清性激素水平、空腹葡萄糖和胰岛素、甘油三酯和胆固醇、性激素结合蛋白和脂联素水平以及用蛋白印迹法检测卵巢组织p38-MAPK、c-Jun和NF-κB蛋白表达。结果: 与空白组比较,模型组大鼠体重显著增加(P＜0.05),子宫指数显著降低(P＜0.05),囊状卵泡数量显著增加(P＜0.05),血清黄体生成素(LH)、睾酮(T)水平和LH/FSH比值显著升高(P＜0.05),卵泡刺激素(FSH)水平显著下降(P＜0.05),总胆固醇(TC)、甘油三酯(TG)、空腹胰岛素和胰岛素指数(HOMA)显著增加(P＜0.05),性激素结合蛋白(SHBG)含量显著减少以及脂联素(LPS)含量显著增加(P＜0.05),卵巢组织p38-MAPK、c-Jun和NF-κB蛋白表达上调(P＜0.05)。与模型组比较,黄连素能显著增加子宫指数(P＜0.05)、次级卵泡数量(P＜0.05),显著降低血清促黄体生成素(LH)水平、睾酮(T)水平和LH/FSH比值(P＜ 0.05),显著下调卵巢组织p38-MAPK和NF-κB蛋白表达(P＜0.05),作用类似达英-35;黄连素能明显降低血清甘油三酯(TG)、胰岛素水平和胰岛素指数(P＜0.05),升高血清SHBG水平,降低LPS水平(P＜0.05),作用类似二甲双胍。结论: 黄连素通过下调卵巢组织p38-MAPK和NF-κB蛋白表达,降低血清LPS含量,起到调控PCOS大鼠性激素紊乱和胰岛素抵抗(IR)的作用。

关键词: 多囊卵巢综合征(PCOS), 脂联素(LPS), 黄连素, p38-MAPK, NF-κB, c-Jun蛋白, 大鼠

Abstract: Objective: To investigate the effects of berberine on glucose and lipid metabolism, sex hormone binding protein, adiponectin (LPS), NF-κB and MAPK signaling pathways in polycystic ovary syndrome (PCOS) model rats. Methods: Female SD rats were randomly divided into control group, PCOS model group, berberine (0.216 g/kg) group, metformin (0.135 g/kg) group and Dyne-35 (0.18 mg/kg) group, 10 rats in each group. The rats in PCOS model group were treated with letrozole 1 mg.kg^-1 by ig for 3 weeks. After 28 days of drug intervention, the body constitution, ovarian and uterine indexes of the rats were detected, and the changes in the number of ovarian follicles were observed by HE staining. The levels of serum sex hormone, glucose and insulin, triglyceride and cholesterol, sex hormone-binding protein and adiponectin were determined by ELISA, and the protein expressions of p38-MAPK, C-Jun and NF-κB in ovarian tissues were determined by Western blot. Results: Compared with control group, body weight of model group was increased (P＜0.05), and uterine index was decreased (P＜0.05); The number of follicles was increased (P＜0.05). Serum levels of luteinizing hormone (LH), testosterone (T) and LH/FSH ratio were increased (P＜0.05), follicular estrogen (FSH) level was decreased (P＜0.05), total cholesterol (TC), triglyceride (TG), fasting insulin and insulin index (HOMA) were increased (P＜ 0.05). The content of sex hormone binding protein (SHBG) was decreased and the content of adiponectin (LPS) was increased (P＜0.05). The protein expressions of p38-MAPK, c-Jun and NF-κB in ovarian tissue were up-regulated (P＜0.05). Compared with model group, in berberine group, the uterine index and the number of secondary follicles were increased(P＜0.05), the serum levels of luteinizing hormone (LH) , testosterone (T) and the ratio of LH/FSH were decreased (P＜0.05), and the protein expression levels of p38-MAPK and NF-κB in ovarian tissue were down-regulated (P＜0.05), which were similar to those of Dyne-35 group. Berberine significantly decreased serum triglyceride (TG), insulin level and insulin index (P＜0.05), increased serum SHBG level and decreased serum LPS level (P＜0.05), which were similar to those of metformin. Conclusion: Berberine can regulate sex hormone disorder and insulin resistance (IR) in PCOS rats by down-regulating the expressions of p38-MAPK and NF-κB protein in ovarian tissues and decreasing the serum content of LPS.

Key words: polycystic ovary syndrome (PCOS), adiponectin (LPS), berberine, p38-MAPK, NF-κB, c-Jun protein, Rat

中图分类号:

R711.5

赵粉琴, 赵艳, 刘洁颖, 苟雅姣, 杨永琴. 黄连素对PCOS模型大鼠LPS /NF-κB、MAPK信号通路的影响^*[J]. 中国应用生理学杂志, 2022, 38(2): 181-186.

ZHAO Fen-qin, ZHAO Yan, LIU Jie-ying, GOU Ya-jiao, YANG Yong-qin. Effects of berberine on LPS /NF-κB and MAPK signaling pathways in PCOS model rats[J]. CJAP, 2022, 38(2): 181-186.

参考文献

[1] Glueck CJ, Goldenberg N. Characteristics of obesity in polycystic ovary syndrome: Etiology, treatment, and genetics[J]. Metabolism, 2019, 92: 108-120.
[2] 宋颖, 李蓉. 多囊卵巢综合征中国诊疗指南解读[J]. 实用妇产科杂志, 2018, 34(10): 737-741.
[3] Patel S.Polycystic ovary syndrome(PCOS),an inflammatory, systemic, lifestyle endocrinopathy[J]. J Steroid Biochem Mol Biol, 2018, 182: 27-36.
[4] Cooney LG, Dokras A.Cardiometabolic risk in polycystic ovary syndrome:Current guidelines[J]. Endocrinol Metab Clin North Am, 2021, 50(1): 83-95.
[5] 郭锐, 秦卫帅, 张双勇, 等. 加味逍遥散对LPS诱导的抑郁模型大鼠海马小胶质细胞TLR4/NF-κB通路的影响[J]. 中国应用生理学杂志, 2020, 36(4): 354-357.
[6] Zhou DN, Li SJ, Ding JL, et al. MIF May participate in pathogenesis of polycystic ovary syndrome in rats through MAPK signalling pathway[J]. Curr Med Sci, 2018, 38(5): 853-860.
[7] 孙淼, 祝鑫瑜, 孟小钰, 等. 基于LPS/TLR4/NF-κB信号通路探讨中药治疗多囊卵巢综合征慢性低度炎症研究进展[J]. 中华中医药学刊, 2021, 39(8): 128-132.
[8] 李萍, 梁琳琅, 王宇, 等. 二甲双胍和西格列汀对胰岛素抵抗糖尿病前期KKAy小鼠胰岛β细胞功能的影响[J]. 中国应用生理学杂志, 2021, 37(6): 644-650.
[9] Glintborg D.Endocrine and metabolic characteristics in polycystic ovary syndrome[J]. Dan Med J, 2016, 63(4): 5232-5260.
[10] 李春林, 张翥, 曾荣荣, 等. 黄连水提物对LPS诱导的猪肠道上皮细胞IL-1β、IL-6、TNF-α mRNA表达及NF-κB/MAPK信号通路的调控作用[J]. 中国兽医学报, 2020, 40(2): 361-368.
[11] 何淑霞, 俞峭拔, 何淑敏, 等. 黄连素对伴胰岛素抵抗的多囊卵巢综合征大鼠卵巢状态的影响[J]. 中国临床药理学杂志, 2020, 36(14): 2045-2048.
[12] Li W, Li D, Kuang H, et al. Berberine increases glucose uptake and intracellular ROS levels by promoting Sirtuin 3 ubiquitination[J]. Biomed Pharmacother, 2020, 121: 109563(1-10).
[13] 范春芳, 郭一沙, 王嘉欢, 等. 黄连素对糖尿病大鼠胰岛素抵抗的治疗作用[J]. 中国应用生理学杂志, 2020, 36(6): 561-564.
[14] 赵颖, 杨园园, 杜雅薇, 等. 黄连素治疗血脂异常有效性和安全性随机对照临床试验的系统评价与Meta分析[J]. 中国中药杂志, 2020, 45(3): 664-673.
[15] 李菲, 张宁, 周冠伦. 肠道菌群与多囊卵巢综合征的免疫学机制研究进展[J]. 现代妇产科进展, 2018, 27(4): 308-310.
[16] 张瑜, 路青华, 曹海芳, 等. GPR81激动剂对非酒精性脂肪肝病大鼠胰岛素抵抗的影响[J]. 中国应用生理学杂志, 2021, 37(4): 354-358.
[17] Kobayashi M, Yoshino O, Nakashima A, et al. Inhibition of autophagy in theca cells induces CYP17A1 and PAI-1 expression via ROS/p38 and JNK signalling during the development of polycystic ovary syndrome[J]. Mol Cell Endocrinol, 2020, 508: 110792.
[18] Wei W, Zhao H, Wang A, et al. A clinical study on the short term effect of berberine in comparison to metformin on the metabolic characteristics of women with polycysticovary syndrome[J]. Eur J Endocrinol, 2012, 66(1): 99-105.
[19] Xie L, Zhang D, Ma H, et al. The effect of berberine on reproduction and metabolism in women with polycystic ovary syndrome:A systematic review and meta-analysis of randomized control trials[J]. Evid Based Compl Alt Med, 2019, 2019: 1-14.
[20] 常惠, 吴效科. 黄连素对PCOS治疗作用及相关机制研究进展[J]. 现代妇产科进展, 2017, 26(3): 235-237.
[21] Akintayo CO, Johnson AD, Badejogbin OC, et al. High fructose-enriched diet synergistically exacerbates endocrine but not metabolic changes in letrozole-induced polycystic ovarian syndrome in Wistar rats[J]. Heliyon, 2021, 7(1): 5890-5897.

黄连素对PCOS模型大鼠LPS /NF-κB、MAPK信号通路的影响^*

Effects of berberine on LPS /NF-κB and MAPK signaling pathways in PCOS model rats

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	王肖婷, 汤一冰, 林青青, 王新雨, 宋正阳, 郝卯林, 钱巍, 王万铁. 细胞自噬在大鼠肺缺血/再灌注引发肝脏损伤中的作用^*[J]. 中国应用生理学杂志, 2022, 38(2): 102-107.
[2]	徐昌顺, 林春, 蔡振宇. 鞘内注射干扰素调节因子8小干扰RNA对术后持续性疼痛大鼠痛阈及脊髓小胶质细胞活化的影响^*[J]. 中国应用生理学杂志, 2022, 38(2): 113-118.
[3]	林佩瑶, 宋英, 秦东旭, 卢栋泽, 范徐丽. 依达拉奉对毒死蜱所致大鼠脑损伤的保护作用及其机制^*[J]. 中国应用生理学杂志, 2022, 38(2): 163-168.
[4]	吴霞, 张玉蓉, 朱晓宁, 汪静. 利用NASH大鼠原代肝细胞与原代Kupffer细胞共培养建立NASH原代细胞模型^*[J]. 中国应用生理学杂志, 2022, 38(2): 187-192.
[5]	徐畅, 吴晓玲, 程凯, 李娜. 完全弗氏佐剂诱导大鼠慢性骨盆疼痛综合征炎性痛模型的制备^*[J]. 中国应用生理学杂志, 2022, 38(1): 6-10.
[6]	郭亚净, 任静, 刘寒, 李亭亭, 张帅, 王洪. MCC950对脑出血大鼠神经损伤的作用^*[J]. 中国应用生理学杂志, 2022, 38(1): 11-16.
[7]	吕栋辉, 安方玉, 颜春鲁, 李海龙, 王嘉玉, 石瑶, 袁灵青, 赵延真, 杨建新, 郭丹, 颉旺军. 中风胶囊对脑缺血/再灌注损伤模型鼠脑组织自噬相关蛋白表达的影响^*[J]. 中国应用生理学杂志, 2022, 38(1): 25-31.
[8]	汪宗保, 王连, 柳奇奇, 杨永晖, 刘攀, 李斯亮, 姚长风. 不同频率的振动训练对大鼠早期膝骨关节炎关节软骨的修复作用及其JNK/NF-κB、SOX9机制^*[J]. 中国应用生理学杂志, 2022, 38(1): 41-46.
[9]	张媛, 盛蕾, 刘小玮, 韦娟, 刘秀娟, 张念云, 王子艺. 不同运动方式对肥胖大鼠肝脏脂质沉积及FGF21分泌的影响^*[J]. 中国应用生理学杂志, 2022, 38(1): 47-52.
[10]	李少情, 张青山, 赵婷, 白婷婷, 宣丽颖, 王羽, 赵明. 黄芪注射液对缺血性心肌病大鼠心肌的保护作用^*[J]. 中国应用生理学杂志, 2022, 38(1): 75-78.
[11]	张利娜, 杜相欣, 张雨彤, 郭霞, 郝娜, 赵欣, 张宇. 微丝电极阵列的参考电极内置与外置的对比研究^*[J]. 中国应用生理学杂志, 2022, 38(1): 85-90.
[12]	张雨彤, 赵欣, 尹艺儒, 吴淑芬, 张利娜, 杜相欣, 张宇. 老年大鼠脊髓小胶质细胞分选新方法及功能特征观察^*[J]. 中国应用生理学杂志, 2022, 38(1): 91-96.
[13]	汤娟, 柯洁, 付裕, 何晓伟, 李先伟. Ⅱ型肺泡上皮细胞间质转分化中的Notch-1/ Twist-1信号通路机制^*[J]. 中国应用生理学杂志, 2021, 37(6): 577-583.
[14]	齐书妍, 黄华, 李永坤, 裴林国, 张文娟. 莪术醇对非酒精性脂肪性肝大鼠肝功能和肝纤维化的影响及机制^*[J]. 中国应用生理学杂志, 2021, 37(6): 611-615.
[15]	朱海东, 吕长坤, 马菲菲. 牛磺酸上调基因1(TUG1)对肝纤维化的作用及其机制^*[J]. 中国应用生理学杂志, 2021, 37(6): 616-621.