Objective To investigate the value of cardiovascular autonomic reflex test(CART) and heart rate variability(HRV) for the diagnosis of diabetic cardiac autonomic neuropathy(DCAN). Methods A total of 154 hospitalized patients with type 2 diabetes mellitus(T2DM) in Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine from Feb. to Dec. 2020 were enrolled. All patients underwent CART and 24-h Holter monitoring, and HRV indexes were analyzed. The differences in diagnostic value of DCAN between CART and HRV were analyzed. Results Among the 154 T2DM patients, 101 in the DCAN group and 53 in the non-DCAN group were diagnosed using CART. The incidence of DCAN was 65.58%(101/154). The differences in age, diabetes mellitus duration and incidence of diabetic peripheral neuropathy were statistically significant between DCAN and non-DCAN groups(all P<0.05), while the differences in gender, hypertension, smoking or drinking habits, body mass index, waist-to-hip ratio,glycated albumin or brain natriuretic peptide were not statistically significant(all P>0.05). There were significant differences in expiration/inspiration difference, 30/15 ratio, Valsalva test and blood pressure differences after postural change between the 2 groups(all P<0.05). There were significant differences in HRV indexes(standard deviation of all normal N-N interval [SDNN], mean standard deviation of the normal N-N interval every 5 min [SDANN], root mean square of successive differences between adjacent N-N intervals [RMSSD], percentage of the number of pairs of adjacent N-N intervals differing by more than 50 ms [pNN50], total power [TP], very low frequency [VLF], low frequency [LF], and high frequency [HF])(all P<0.05). The incidence of DCAN was 59.74%(92/154) according to the HRV indexes of 24-h Holter. The total coincidence rate was 61.68% between HRV and CART, and Kappa value was 0.184. The sensitivity and specificity of HRV in diagnosing DCAN were 66.34% and 52.83%, respectively. According to the CART score, T2DM patients were divided into 4 grades: non-, sub-clinical, confirmed and severe DCAN. The degree of DCAN was negatively correlated with SDNN,SDANN, RMSSD, pNN50, TP, VLF, LF, and HF(r=-0.252,-0.234,-0.260,-0.219,-0.315,-0.280,-0.316 and-0.311, all P<0.01). The correlation analysis of HRV indexes in the DCAN patients diagnosed by CART found that SDNN and SDANN had the strongest correlation(r=0.977, P<0.001), suggesting that sympathetic nerve damage was obvious; correlations between LF and VLF(r=0.761, P<0.001) and HF(r=0.829, P<0.001) were strong, suggesting that sympathetic and parasympathetic nerves were involved in cardiac autonomic damage. CART combined with HRV diagnosed 134 cases in the DCAN group and 20 cases in the non-DCAN group, and the incidence of DCAN was 87.01%(134/154).The sensitivity and specificity of CART combined with HRV in diagnosing DCAN were 100.00% and 37.74%, respectively.Conclusion CART combined with HRV has a higher detection rate in the diagnosis of DCAN. HRV analysis can be further performed on T2DM patients with low CART score at the early stage of DCAN to reduce the incidence of missed diagnosis.
目的 观察参芪补胰方对2型糖尿病(type2diabetesmellitus,T2DM)大鼠TLR4/MyD88/NF-κB信号通路的影响,探讨参芪补胰方治疗T2DM的作用机制。方法 采用随机对照法将48只SD大鼠随机分为7组,正常组予以基础饲料喂养,其余各组动物采用高糖高脂饲养加腹腔注射STZ法造模,二甲双胍组给予盐酸二甲双胍片,中药组给予不同剂量参芪补胰方,给药6周后留取标本。ELISA法检测大鼠肿瘤坏死因子-α(TumorNecrosisFactor,TNF-α)、白细胞介素-1β(Interleukin1β,IL-1β)、白细胞介素-10(Interleukin10,IL-10)、白细胞介素-17(Interleukin17,IL-17)水平,HE染色法观察大鼠胰腺组织病理变化,TUNEL染色法观察大鼠胰岛细胞凋亡情况,RT-PCR法检测大鼠胰腺组织TLR4、MyD88、NF-κB的mRNA表达水平,Westernblot法检测大鼠胰腺组织TLR4、MyD88、NF-κB的蛋白表达水平。结果 参芪补胰方对DM大鼠FBG水平方面有明显下降作用,与模型组比较有统计学差异(P<0.05);参芪补胰方组大鼠血清TNF-α、IL-1β、IL-10、IL-17表达水平明显降低(P<0.05);可以通过改善大鼠胰腺组织损伤、促进细胞结构组织修复、减少细胞凋亡起到抗T2DM的作用;同时,与模型组比较,参芪补胰方组大鼠胰腺组织TLR4、MyD88、NF-κBmRNA及蛋白表达均明显降低(P<0.05)。结论 参芪补胰方可能通过调控T2DM大鼠炎症因子及TLR4、MyD88、NF-κB表达发挥其抗T2DM的作用。
2型糖尿病(T2DM)的发病机制与胰岛素抵抗(IR)密切相关,胰岛素主要作用于肝脏、脂肪和骨骼肌,它通过与胰岛素受体结合而激活磷脂酰肌醇-3-激酶/蛋白激酶B(PI3K/Akt)信号通路.葡萄糖转运蛋白4(GLUT4)是胰岛素依赖性蛋白,主要负责胰岛素刺激的葡萄糖摄取,同时也是PI3K/Akt信号通路下游的靶蛋白.鉴于PI3K/Akt/GLUT4通路在葡萄糖代谢中的重要调控作用,该文通过检索2006年1月—2022年1月中国知网(CNKI)、维普数据库(VIP)、万方中华医学会期刊数据库、PubMed等数据库中的相关文献,旨在对近5年中药调节PI3K/Akt/GLUT4信号通路治疗T2DM的研究做一总结,以期为中药防治T2DM提供一定的理论基础.
目的 分析2型糖尿病(T2DM)患者心脏自主神经病变的相关危险因素.方法 采取随机抽样法选择2020年2—12月于上海中医药大学附属上海市中西医结合医院内分泌科住院的154例T2DM患者作为研究对象,患者均接受心血管反射试验,以心血管反射试验为诊断糖尿病心脏自主神经病变(DCAN)的金标准,分为DCAN组和无DCAN组,同时记录患者一般资料及生化指标等,分析DCAN的相关危险因素及对DCAN发生发展的预测价值.结果 154例T2DM患者中,DCAN患者101例,无DCAN患者53例,DCAN发生率为65.6%(101/154).两组间年龄、糖尿病病程比较差异有统计学意义(P<0.01),DCAN组糖尿病周围神经病变比例、胱抑素C(CysC)水平高于无DCAN组[75.25%(76/101)比56.60%(30/53),0.87(0.78,0.99)mg/L比0.79(0.73,0.92)mg/L](χ2=5.632,P=0.018;Z=2.808,P=0.005),空腹C肽(FCP)低于无DCAN组[(1.86±0.95)μg/L比(2.34±1.12)μg/L](t=2.817,P=0.005).两组性别、高血压比例、体质指数、总胆固醇、三酰甘油、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、肿瘤坏死因子-α、神经元特异性烯醇化酶、同型半胱氨酸(Hcy)、糖化血红蛋白、血肌酐、尿酸、空腹血糖、餐后2 h血糖(2 h PG)比较差异均无统计学意义(P>0.05).多因素Logistic回归分析结果显示:Hcy、2 h PG、FCP均为DCAN的独立影响因素(OR=1.272,95%CI 1.078~1.501;OR=1.098,95%CI 1.003~1.201;OR=0.528,95%CI 0.335~0.832,P<0.05或P<0.01).受试者工作特征曲线分析显示,Hcy、2 h PG、FCP的曲线下面积分别为0.574、0.564、0.627.结论 Hcy、2 h PG、FCP均为DCAN的独立影响因素,三者AUC面积均处于0.5~0.7,对诊断DCAN具有一定预测价值.
目的:基于中医证素辨证体系探讨糖尿病心脏自主神经病变的中医证型分布,为糖尿病心脏自主神经病变的辨证论治提供参考依据.方法:纳入101例糖尿病心脏自主神经病变患者,制定四诊信息采集表,建立数据库,采用因子分析、聚类分析等统计学方法及中医证素辨证方法,进行中医证候研究.结果:通过因子分析共获得16个公因子,进一步结合中医理论及临床知识进行聚类,依据证素辨证的方法共获得6个病性及3个病位证素,分别为气虚、血虚、阴虚、阳虚、热、血热与心、脾、肝.结论:对分析得出的病性及病位证素进行组合,获得4种有效中医证型,分别为阴虚热盛证、脾阳不振证、心气亏虚证及肝肾阴虚证.
糖尿病心脏自主神经病变(cardiac autonomic neuropathy of diabetes mellitus,DCAN)是糖尿病慢性并发症之一,其发病率逐年增高,但因无特异性症状及体征,故诊断率低.临床常可见静息性心动过速、运动不耐受、体位性低血压、沉默性心肌缺血等症状,严重DCAN时可出现恶性心律失常、心肌梗死和心源性猝死,大大增加了糖尿病患者的死亡风险.西医目前尚无有效的治疗措施,主要从降糖、营养神经、抗氧化和改善微循环等方面入手.中医学对DCAN的探索历史悠远,对其病因病机的论述颇多,各家侧重点虽有不同,但普遍认为与心的气血阴阳亏虚有关.治疗方面多从益气温阳,滋阴通脉,活血化瘀,宁心定悸,调和营卫等出发.通过使用经方、验方、中成药、针灸推拿、贴敷等显著改善了DCAN患者临床症状及其评价指标.文章就糖尿病心脏自主神经病变的中医药研究现状,包括病因病机、辨证论治、内治、外治等方面做一浅述.
目的 探讨miRNA-455-3p在糖尿病肾病(DKD)大鼠肾小球硬化过程中的作用,以及厄贝沙坦对这一过程的影响.方法 miRNA-455-3p激动剂干预实验:雄性SD大鼠18只,随机取其中6只作为对照组;其余12只大鼠采用高脂高糖饲料喂养及链脲佐菌素(STZ)30 mg/kg腹腔注射制备DKD模型,造模成功后随机分为模型组(STZ组)和过表达miRNA-455-3p组(STZ+miRNA-455-3p组),每组6只,其中STZ+miRNA-455-3p组在STZ注射后第2周和第5周时以20 mg/kg的剂量腹腔注射miRNA-455-3p激动剂.厄贝沙坦干预实验:雄性SD大鼠18只随机分为对照组、模型组(STZ组)、厄贝沙坦干预组(STZ+厄贝沙坦组),每组6只,其中STZ+厄贝沙坦组予以50 mg/kg的厄贝沙坦悬浊液灌胃.所有大鼠均于12周后记录24 h尿量、24 h尿蛋白水平,采用qRT-PCR法检测各组大鼠血清及肾组织中miRNA-455-3p的表达水平,过碘酸希夫染色法观察大鼠肾组织病理改变,蛋白质印迹法检测肾组织中胶原蛋白Ⅰ和增殖细胞核抗原(PCNA)蛋白表达水平.结果 STZ+miRNA-455-3p组及STZ+厄贝沙坦组大鼠24 h尿量、24 h尿蛋白水平均较STZ组降低,差异均有统计学意义(P均<0.05);STZ+miRNA-455-3p组及STZ+厄贝沙坦组大鼠血清及肾组织中miRNA-455-3p表达水平均较STZ组升高,差异均有统计学意义(P均<0.05);STZ+miRNA-455-3p组及STZ+厄贝沙坦组大鼠肾组织中胶原蛋白Ⅰ、PCNA表达均较STZ组减少,差异均有统计学意义(P均<0.05).结论 miRNA-455-3p参与DKD进程,可能是DKD治疗的新靶点,而厄贝沙坦能够通过调控miRNA-455-3p表达延缓DKD肾小球硬化进程.
Diabetic nephropathy (DN) is among the common complications of diabetes and is a major cause of end-stage kidney disease. Emerging data indicate that renal inflammation is involved in DN progression and aggravation. Still, the exact cellular mechanisms remain unclear. Dysregulated expression of microRNAs (miRNAs) is associated with multiple diseases, including DN. The relationship between miRNAs and inflammation in DN is also unexplored. Here, we evaluated the role of miR-485 in mediating the response of human mesangial cells (HMCs) to a high glucose (HG) concentration, and the potential underlying mechanism. We found that miR-485 expression is significantly decreased in HG-stimulated HMCs. Overexpression of miR-485 suppressed HG-induced proliferation of HMCs. Lower production of proinflammatory cytokines (i.e., TNF-α, IL-1β, and IL-6) was observed in miR-485-overexpressing HMCs. Overexpression of miR-485 markedly suppressed the overexpression of extracellular-matrix proteins, e.g., collagen IV (Col IV) and fibronectin (FN), in HG-stimulated HMCs. Furthermore, miR-485 suppressed the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 5 (NOX5), restrained the HG-induced HMC proliferation, downregulated the expression of proinflammatory cytokines, and inhibited the production of extracellular-matrix proteins in HMCs. These results provide new insights into the involvement of the miR-485-NOX5 signaling pathway in DN progression.