Effects of Chinese Fructus Mume Formula and Its Separated Prescription Extract on Insulin Resistance in Type 2 Diabetic Rats

The effect of Fructus Mume formula and its separated prescription extract on insulin resis- tance in type 2 diabetic rats was investigated. The rat model of type 2 diabetes was established by feed- ing on a high-fat diet for 8 weeks and by subsequently intravenous injection of small doses of strepto- zotocin. Rats in treatment groups, including the Fructus Mume formula treatment group （FM）, the cold property herbs of Fructus Mume formula treatment group （CFM）, the warm property herbs of Fructus Mume formula treatment group （WFM）, were administrated with Fructus Mume formula and its sepa- rated prescription extract by gavage, while the rats in diabetic model group （DM） and metformin group （MET） were given by gavage with normal saline and metformin correspondingly. The body weight be- fore and after treatment was measured, and the oral glucose tolerance test （OGTT） and the insulin re- lease test （IRT） were performed. The homeostasis model assessment-insulin resistance index （HOMA-IR） was calculated. The protein and mRNA expression levels of Insr, β-arrestin-2, Its-1 and Glut-4 in the liver, skeletal muscle and fat tissues were detected by using Western blotting and RT-PCR respectively. The results demonstrated that, as compared with DM group, OGTT, IRT （0 h, 1 h） levels and HOMR-IR in treatment groups were all reduced, meanwhile their protein and mRNA expression levels of Insr, Irs-1 and Glut-4 in the liver, skeletal muscle and fat tissues were obviously increased, and their protein and mRNA expression levels of β-arrestin-2 in the liver and skeletal muscle tissues were also markedly increased. It was suggested that the Fructus Mume formula and its separated prescription extracts could effectively improve insulin resistance in type 2 diabetic rats, which might be related to the up-regulated expression of Insr, Irs-1 and Glut-4 in the liver, skeletal muscle and fat tissues, and β-arrestin-2 in the liver and skeletal muscle tissues.

基于改进遗传算法的2型糖尿病中医药有效处方推荐方法研究

目的改进遗传算法创新推荐度模型,以2型糖尿病(T2DM)电子病历数据为基础进行核心处方挖掘及有效处方推荐。方法基于真实世界电子病历数据,构建T2DM患者有效处方集及不同证型原始处方集数据库;对遗传算法进行改进,优化适应度函数的构建,使提取出的核心有效处方朝着有效处方集的方向进化;基于核心有效处方与原始处方集的相似度关系,创新推荐度模型,通过遍历不同证型原始处方集进行处方推荐度挖掘。结果共使用有效诊疗标准的处方17712条,提取的核心有效处方中包含中药37种;最终挖掘出满足“推荐度≥85%”的处方26条,最大推荐度为97.26%。结论研究改进遗传算法提高了对中药处方集的特征提取和全局搜索能力,并通过提出新的推荐度模型进行临床处方决策推荐,提高了电子病历数据的利用率。

Investigation on the mechanism of Qiangxinhuoli prescription in the treatment of chronic heart failure based on p38-MAPK signaling pathway

Background:The aim of this study is to investigate the mechanism of action underlying the therapeutic effects of the national patent Chinese medicine compound“Qiangxinhuoli prescription(QXHLF)”on chronic heart failure(CHF).Methods:In vitro,the H_(9)C_(2) cell model was induced by ANGII,and cell proliferation and related protein expression were detected by Cell Counting Kit-8 and Western blot.In vivo,A rat model of CHF was prepared by ligation of the left anterior descending coronary artery.The effects of QXHLF on cardiac function in CHF rats were evaluated by cardiac index,hemodynamic changes,enzyme-linked immunosorbent assay,hematoxylin-eosin staining,immunohistochemistry,Western blot and RT-PCR.The expression of pro-apoptotic factors and anti-apoptotic factors,as well as TGFβ1,p-p38,TAK 1 mRNA,and protein,were detected.Results:In vitro,QXHLF has a significant inhibitory effect on the proliferation of H_(9)C_(2) cells.QXHLF can reduce the expression levels of TAK 1,TGFβ1,p-p38,Caspase3 and BAX proteins in H_(9)C_(2) cells,and increase the expression level of BCL_(2) protein.In vivo,QXHLF has the potential to increase left ventricular systolic pressure,m aximum rate of change in left ventricular pressure while decreasing left ventricular end diastolic pressure,and inhibiting the serum levels of brain natriuretic peptide.Moreover,QXHLF exhibits significant improvements in the pathological alterations of myocardial cells and fibers in CHF rats,leading to enhanced myocardial tissue morphology and notable advantages in combating myocardial fibrosis.QXHLF can reduce the levels of BAX and Caspase3 and up-regulate the expression of BCL_(2),thereby inhibiting cardiomyocyte apoptosis.Furthermore,QXHLF demonstrates inhibitory effects on the mRNA and protein expression levels of TGFβ_(1),TAK_(1),and p-p38 in the heart tissue of the CHF rat model.Conclusion:These findings indicate that QXHLF has a therapeutic effect on CHF by inhibiting the p38-MAPK signaling pathway,reducing myocardial fibrosis,preventing apoptosis,inhibiting cell proliferation,and restoring myocardial injury.

消癌解毒方抑制H22荷瘤小鼠移植瘤生长及调控Bcl-2/CytC信号通路诱导凋亡实验研究

目的探讨消癌解毒方对H22荷瘤小鼠肿瘤生长以及Bcl-2/CytC信号通路中关键蛋白表达的影响。方法构建H22肝癌移植瘤模型,将C57BL/6J小鼠随机分为模型组(生理盐水灌胃)、消癌解毒方低剂量组(10 g·kg^(-1)·d^(-1)灌胃)、消癌解毒方中剂量组(20 g·kg^(-1)·d^(-1)灌胃)、消癌解毒方高剂量组(40 g·kg^(-1)·d^(-1)灌胃)及顺铂组(1 mg·kg^(-1)·d^(-1)腹腔注射),另设空白组(生理盐水灌胃),每组10只。给药11 d,记录各组瘤重,计算抑瘤率,苏木素-伊红(HE)染色观察病理变化,TUNEL试剂盒检测凋亡率,实时荧光定量PCR(Real-time PCR)检测瘤体组织中JAK2、STAT3 mRNA表达情况,蛋白免疫印迹(Western blot)检测瘤体组织Bax、Bcl-2、CytC、Caspase-3、Cleaved Caspase-3蛋白表达情况。结果消癌解毒方高、中、低剂量组及顺铂组均能有效抑制H22荷瘤小鼠瘤体生长,抑瘤率分别为59.9%、34.5%、21.5%、67.1%;病理学改变与模型组相比,给药组病理性核分裂像减少,瘤细胞排列稀疏,表现出较好的抑制作用;TUNEL凋亡检测结果示,消癌解毒方处理后瘤体细胞呈典型凋亡征象,以高剂量组最为显著;Rt-PCR检测发现消癌解毒方干预后各组的JAK2、STAT3 mRNA表达水平下调;Western blot检测发现消癌解毒方对H22荷瘤小鼠干预后,可下调Bcl-2蛋白表达,上调Bax、CytC、Cleaved Caspase-3蛋白表达,最终激活Caspase-3蛋白,诱导肿瘤细胞凋亡。结论消癌解毒方可抑制H22荷瘤小鼠生长及诱导肝癌细胞凋亡,这可能与调控Bcl-2/CytC信号通路中关键蛋白表达相关,从而发挥抗肿瘤作用。

Network Pharmacology Approach to Investigate the Preventive Mechanism of Hunan Expert Group Recommended Chinese Medicine Prevention No.2 Prescription Against COVID-19

Objective To explore the possible preventive mechanism of Hunan expert group recommended Chinese medicine prescription of No.2(Pre-No.2)against coronavirus disease 2019(COVID-19)by network pharmacology method.Methods The target proteins of effective components and active compounds in Pre-No.2 were screened by searching the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).A component-target-disease interaction network of Pre-No.2 was constructed by Cytoscape 3.7.2,gene ontology(GO)analysis,and Kyoto encyclopedia of genes and genomes(KEGG)analysis of target protein pathway by DAVID.Results A total of 163 compounds and 278 target protein targets in Pre-No.2 were collected from the TCMSP database.Kaempferol,wogonin,7-methoxy-2-methyl isoflavone,formononetin,isorhamnetin,and licochalcone A were the most frequent targets in the regulatory network.GO enrichment analysis showed that Pre-No.2 regulated response to virus,viral processes,humoral immune responses,defense responses to virus and viral entry into host cells.KEGG enrichment analysis showed that the formula regulated the NF-κB signaling pathway,B cell receptor signaling pathway,viral carcinogenesis,T cell signaling pathway and FcγR-mediated phagocytosis signaling pathway.Conclusions Pre-No.2 may play a preventive role against COVID-19 through regulation of the Toll-like signaling,T cell signaling,B cell signaling and other signaling pathways.It may regulate the immune system to protect against anti-influenza virus.

An exploration on the protective mechanism of Xuduan Zhongzi prescription against epididymis oxidative damage in oligoasthenospermia model rats based on Nrf2-NQO1/γ-GCS signaling pathway

Objective:To investigate the protective mechanism of Xuduan Zhongzi prescription against epididymal oxidative damage in oligoasthenospermia model rats.Methods:Forty SD rats were randomly divided into blank group,model group,Xuduan Zhongzi prescription group(10g/kg)and L-carnitine group(0.1g/kg).Except blank group,all induced oligoasmospermia.The blank group and model group were given normal saline intragastric administration,the Xuduan Zhongzi prescription group was given Xuduan Zhongzi prescription solution intragastric administration,and the L-carnitine group was given L-carnitine intragastric administration.HE staining was used to observe the epididymis structure after 8 weeks.The concentration and activity rate of epididymis sperm were measured by sperm quality.MRNA and protein expression levels of Nrf2,NQO1 andγ-GCs in epididymis were detected by RT-qPCR and immunohistochemistry.Results:①HE staining:in the blank group,the epididymis tubes were arranged tightly and regularly,the tissue structure was complete,the epithelial cells were arranged orderly,and the lumen sperm were numerous and evenly distributed.The epididymis of model group showed structural atrophy,loose arrangement,enlarged mesenchyme,increased cell debris and significantly reduced sperm cells.Compared with the model group,the lumen lesions of epididymis in Xuduan Zhongzi prescription group and L-carnitine group were significantly improved,and the amount of normal sperm in lumen was increased and the distribution was uniform.②Results of sperm quality comparison among each group:sperm density and sperm motility rate:compared with blank group,sperm density and sperm motility rate in other groups were significantly decreased(P<0.05),and sperm density and sperm motility rate in model group were significantly decreased(P<0.05);Compared with model group,the sperm density and motility rate in Xuduan Zhongzi prescription group and L-carnitine group were significantly increased(P<0.05).③RT-qPCR and immunohistochemistry:Compared with the blank group,the mRNA and protein levels of Nrf2,NQO1 andγ-GCs in epididymal rats in model group were significantly decreased(P<0.05),while the mRNA and protein levels of Nrf2,NQO1 andγ-GCs were significantly increased in L-carnitine group and Continua seed formula group(P<0.05).Conclusion:Xuduan Zhongzi prescription can reduce oxidative stress damage and improve sperm quality of oligoasthenospermia.The mechanism may related to promoting the activation of Nrf2-NQO1/γ-GCS pathway in epididymis of oligoasthenospermia rats,and up-regulate the expressions of Nrf2,NQO1 andγ-GCS proteins.

养阴运津方联合常规疗法治疗2型糖尿病伴非酒精性脂肪肝临床研究

目的:观察养阴运津方联合常规疗法治疗2型糖尿病(T2DM)伴非酒精性脂肪肝(NAFLD)疗效及对糖脂代谢的影响。方法:选择2022年1月—2023年1月安阳市中医院接受治疗的110例T2DM伴NAFLD气阴两虚证患者,按随机数字表法分为对照组及观察组各55例。过程中对照组和观察组中分别有3例、1例被剔除,最终分别纳入52例、54例。对照组采用常规现代医学治疗,观察组在对照组基础上加用养阴运津方治疗。比较2组治疗前后中医证候评分、糖脂代谢水平、肝功能水平、NAFLD超声分度情况的变化,比较2组不良反应发生情况。结果:治疗1个月及3个月后,2组神疲乏力、口渴多饮及气短自汗中医证候评分均较治疗前下降(P<0.05),观察组上述3项评分均低于同一时间段对照组(P<0.05)。治疗1个月及3个月后,2组空腹血糖、餐后2 h血糖及糖化血糖蛋白水平均较治疗前下降(P<0.05),观察组上述3项水平均低于对照组(P<0.05)。治疗1个月及3个月后,2组甘油三酯、胆固醇水平均较治疗前下降,高密度脂蛋白胆固醇水平均较治疗前升高,差异均有统计学意义(P<0.05);观察组甘油三酯、胆固醇水平均低于对照组,高密度脂蛋白胆固醇水平高于对照组,差异均有统计学意义(P<0.05)。治疗1个月及3个月后,2组谷草转氨酶、谷丙转氨酶、谷氨酰基转移酶水平均较治疗前下降(P<0.05),观察组上述3项水平均低于同一时间段对照组(P<0.05)。治疗3个月后,2组NAFLD超声分度重度比例较治疗前降低,NAFLD超声分度轻度比例均较治疗前升高,治疗后,观察组NAFLD超声分度轻度比例高于对照组、重度比例低于对照组(P<0.05)。对照组不良反应发生率为5.77%(3/52),观察组不良反应发生率为9.26%(5/54),2组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:养阴运津方联合常规疗法治疗T2DM伴NAFLD可有效控制临床病情,改善糖脂代谢,保护肝脏功能,降低肝脏脂肪沉积,安全性良好。

复合絮凝剂XG-2的制备及应用研究

利用铝型材下脚料研制一种廉价的复合絮凝剂XG 2 ,研究制备过程中最佳酸溶浓度、酸溶时间、聚合活化条件等因素对絮凝剂的性能的影响 ,建立简单易于操作的制备工艺流程 .应用于造纸、毛巾厂工业废水处理 。

2XG-4型干式真空泵的研制

本文着重阐述了 ２ＸＧ－４型干式真空泵研制的重大意义、泵的结构设计、旋片及密 封等材料的选用上所做的研究和试验工作，并以理想的测试结果证实了该泵设计的新颖 性和合理性。

丹藤通脉方治疗2型糖尿病周围神经病变患者的临床疗效观察

目的:探讨丹藤通脉方用于治疗2型糖尿病周围神经病变的临床疗效。方法:选择2019年1月-2021年12月在南京中医药大学附属徐州市中医院内分泌科住院治疗的2型糖尿病周围神经病变患者60例;采用随机法将上述患者分为观察组和对照组(每组30例);对照组给予基础治疗联合甲钴胺治疗,观察组在对照组治疗基础上给予联合丹藤通脉方治疗。治疗周期共12周,对比两组疗效。结果:治疗后组间效果比较,观察组患者的总有效率高于对照组(P<0.05)。多伦多临床评分系统(Troronto Clinical Scoring System,TCSS)评分低于对照组(P<0.05);空腹血糖(Glucose,GLU)、餐后2小时血糖(2-hour Postprandial Blood Glucose,2 h PG)、糖化血红蛋白(Hemoglobin A1c,HbA1c)水平低于对照组(P<0.05);总胆固醇(Total Cholesterol,TC)、三酰甘油(Triglycerides,TG)、低密度脂蛋白(Low Density Lipoprotein,LDL)水平低于对照组(P<0.05);右腓神经及正中神经的运动神经传导速度(Sensory Nerve Conduction Velocity,SNCV)和感觉神经传导速度(Motor Nerve Conduction Velocity,MNCV)高于对照组(P<0.05)。与治疗前比较,观察组和对照组治疗后的TCSS、GLU、2 h PG、HbA1c水平及TC、TG、LDL水平均降低(P<0.05),右腓神经及正中神经的MNCV和SNCV均升高(P<0.05)。结论:丹藤通脉方治疗糖尿病周围神经病变患者疗效确切,安全性良好,值得进一步推广。

基于NOX5-ERK1/2信号通路探讨健脾祛痰化瘀方对动脉粥样硬化小型猪炎症反应的影响

目的 观察健脾祛痰化瘀方对动脉粥样硬化(AS)小型猪氧化应激和炎症反应的影响,基于NOX5-ERK1/2信号通路探讨其作用机制。方法 将12只巴马小型猪随机分为对照组、模型组和健脾祛痰化瘀方低、高剂量组,每组3只。采用高脂饮食饲养24周构建动脉粥样硬化模型,给药组同时在饲料中添加健脾祛痰化瘀方。分别于给药0、16、24周检测小型猪一般体征(体长、腹围、体质量、食物摄入量和粪便含水量),HE染色观察主动脉形态,油红O染色观察主动脉和心肌组织脂质沉积,透射电镜观察胸主动脉组织超微结构,全自动生化分析仪检测血清总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)含量,ELISA检测血清活性氧(ROS)、白细胞介素(IL)-6、IL-10、肿瘤坏死因子(TNF)-α、超敏C反应蛋白(hs-CRP)、血管细胞黏附分子-1(VCAM-1)、细胞间黏附分子-1(ICAM-1)含量,Western blot检测主动脉组织NADPH氧化酶5(NOX5)、细胞外信号调节激酶1/2(ERK1/2)、p-ERK1/2、VCAM-1、增殖细胞核抗原(PCNA)蛋白表达。结果 与正常组比较,模型组小型猪16、24周腹围、体质量、食物摄入量增加(P<0.01),主动脉内膜明显增厚,内皮细胞破坏,脂质沉积,平滑肌细胞水肿,线粒体肿胀明显,血清TC、LDL-C含量及ROS、IL-6、IL-10、TNF-α、hs-CRP、VCAM-1、ICAM-1含量升高,HDL-C含量降低(P<0.01);主动脉组织NOX5、p-ERK1/2、VCAM-1、PCNA蛋白表达升高(P<0.01)。与模型组比较,健脾祛痰化瘀方低、高剂量组16、24周腹围、体质量、食物摄入量减少(P<0.05,P<0.01),斑块面积和脂质沉积减少,内皮细胞破坏减轻,血清TC、LDL-C含量及ROS、IL-6、IL-10、TNF-α、hs-CRP、VCAM-1、ICAM-1含量降低,HDL-C含量升高(P<0.01,P<0.05);主动脉组织NOX5、p-ERK1/2、VCAM-1、PCNA蛋白表达降低(P<0.01,P<0.05)。结论 健脾祛痰化瘀方可减轻小型猪AS,其机制可能与抑制NOX5-ERK1/2信号通路激活、减轻氧化应激诱导的炎症反应有关。

温肺降浊方对血管性痴呆模型大鼠ERK1/2信号通路相关蛋白的影响

目的:观察温肺降浊方对血管性痴呆(VaD)模型大鼠细胞外调节蛋白激酶(ERK1/2)信号通路的影响,探讨其治疗VaD可能的相关作用机制。方法:将雄性SD大鼠随机分为假手术组和模型组(等体积0.9%氯化钠溶液灌胃),温肺降浊方低、中、高剂量组(1.5、3、6 ml剂量灌胃)。观察造模后大鼠水迷宫评分和HE病理变化,免疫组化、RT-qPCR和Western blot检测海马组织中ERK1/2、钙蛋白酶(Calpain)、Bcl-2关联死亡启动子重组蛋白(Bad)、B淋巴细胞瘤-xl(Bcl-xl)蛋白和mRNA表达情况。结果:与假手术组相比,模型组和温肺降浊方各剂量组大鼠逃避潜伏期延长、穿越平台次数缩短(P<0.05),海马组织形态稀疏、水肿及核缩小;海马组织ERK1/2、Calpain、Bad蛋白和mRNA表达升高(P<0.05),Bcl-xl蛋白和mRNA表达下降(P<0.05)。与模型组比较,温肺降浊方高剂量组大鼠逃避潜伏期缩短、穿越平台次数增加(P<0.05),海马组织形态逐渐紧密、水肿减少,数量增多;海马组织ERK1/2、Calpain、Bad蛋白和mRNA表达下降(P<0.05),Bcl-xl蛋白和mRNA表达升高(P<0.05)。结论:血管性痴呆可能与大鼠海马中的ERK1/2、Calpain、Bad蛋白升高及Bcl-xl蛋白降低有关,温肺降浊方可以抑制VaD大鼠海马中的ERK1/2通路激活,减少神经细胞凋亡,延缓疾病进展,改善血管性痴呆大鼠的学习记忆能力。

体医融合背景下运动处方护理干预模式对2型糖尿病血糖指标的影响

目的:总结体医融合背景下运动处方护理干预模式对2型糖尿病血糖指标、生存质量、体适能及依从性的影响。方法:2020年8月—2022年6月从北京大学深圳医院康复医学科及周边社康中心共招募2型糖尿病病人106例为研究对象,采用随机数字表法将病人分为试验组、对照组各53例。试验组实施运动处方训练营干预+药物治疗方案,对照组实施家居运动处方+药物治疗方案,比较两组病人干预前后血糖指标、生活质量、体适能及运动依从性。结果:干预后试验组病人空腹血糖、餐后2 h血糖、糖化血红蛋白均低于对照组(P<0.05),生活质量中的躯体疼痛、生理功能、生理职能、社会功能、总体健康评分高于对照组(P<0.05),体适能相关指标中椅子坐下站立、椅子坐姿体前弯曲、举哑铃手臂弯曲与对照组比较差异有统计学意义(P<0.05);试验组病人运动依从性为96.23%,高于对照组的67.92%(P<0.05)。结论:体医融合背景下开展运动处方护理可明显改善2型糖尿病病人血糖指标,提高病人运动依从性,改善病人生活质量及体适能指标。

清养活血2号方治疗老年急性缺血性卒中相关性肺炎气虚痰热瘀阻证临床效果

目的探讨清养活血2号方治疗老年急性缺血性卒中相关性肺炎(SAP)气虚痰热瘀阻证的临床效果。方法选择2021年2月至2022年12月重庆市中医院收治的老年急性缺血性SAP气虚痰热瘀阻证患者66例,采用随机数字表法将其分为观察组(33例)和对照组(33例)。对照组给予规范化治疗,观察组在对照组基础上给予清养活血2号方。治疗10 d后比较两组临床效果,比较两组在治疗前及治疗第5、10天的中医证候积分、美国国立卫生研究院卒中量表评分(NIHSS)、急性生理和慢性健康状况Ⅱ(APACHEⅡ)评分、临床肺部感染评分(CPIS)、全身炎症反应综合征(SIRS)评分、血清降钙素原(PCT)水平。统计两组治疗期间不良反应发生情况。结果观察组临床疗效优于对照组,差异有统计学意义(P<0.05)。两组治疗第5、10天中医证候积分、血清PCT水平、NIHSS、APACHEⅡ评分、SIRS、CPIS均低于治疗前,且治疗第10天低于治疗第5天,差异有统计学意义(P<0.05)。观察组治疗第5、10天中医证候积分及APACHEⅡ评分、SIRS均低于同期对照组,观察组治疗第10天NIHSS、CPIS、血清PCT水平均低于同期对照组,差异有统计学意义(P<0.05)。两组均未发生明确药物过敏、皮肤、药物性肝肾损害及其他不良反应。结论清养活血2号方能够改善老年急性缺血性SAP患者的中医证候,提高整体疗效,安全性较好。

健脾消脂方“异病同治”2型糖尿病与脂代谢紊乱型疾病的作用机制探讨

目的探讨健脾消脂方异病同治2型糖尿病(T2DM)与脂代谢紊乱型疾病的作用机制。方法通过中药系统药理学分析平台(TCMSP)获得健脾消脂方中主要的活性成分及其潜在靶蛋白。利用OMIM、GeneCards和DisGeNET数据库筛选出与T2DM、肥胖(Obesity)和非酒精性脂肪肝(NAFLD)相关的疾病靶点,并通过Cytoscape 3.7.0软件构建“关键靶点蛋白互作”网络图;在DAVID数据库中进行GO富集分析及KEGG通路富集分析。结果检索到健脾消脂方71种活性成分,263个有效靶点,T2DM有效靶点2078个,NAFLD有效靶点2091个,Obesity有效靶点2533个,药物与疾病交集靶点110个。GO与KEGG分析表明健脾消脂方治疗T2DM、NAFLD和Obesity主要涉及的通路有AGE-RAGE糖尿病并发症信号通路、TNF信号通路、IL-17信号通路等;主要涉及的靶点有AKT1、CASP3、TP53、TNF、IL-6、IL-1β。结论健脾消脂方通过健运中州、祛瘀泄浊法异病同治T2DM、NAFLD与Obesity,它的机制可能与改善胰岛素抵抗、炎症反应、脂代谢有关,可广泛应用于T2DM合并脂代谢紊乱型疾病。

健脾益肾方联合非奈利酮治疗2型糖尿病肾病早中期阶段临床研究

目的:观察健脾益肾方联合非奈利酮治疗2型糖尿病肾病早中期阶段的临床效果。方法:选取60例2型糖尿病肾病早中期阶段的患者作为研究对象,采取随机数字表法分为对照组和观察组各30例。2组均给予常规治疗控制血糖、血压,并告知患者适当运动,合理膳食。对照组在常规治疗基础上给予非奈利酮片口服,观察组在对照组基础上给予健脾益肾方治疗。比较2组糖化血红蛋白(HbA1c)、尿素氮(BUN)、估算的肾小球滤过率(eGFR)、尿微量白蛋白/尿肌酐比值(UACR)以及血钾(K)水平。结果:治疗后,2组HbA1c、BUN、eGFR、K比较,差异无统计学意义(P>0.05)。治疗后,2组UACR水平低于治疗前(P<0.05),且观察组UACR水平低于对照组(P<0.05)。结论:健脾益肾方联合非奈利酮治疗糖尿病肾病早中期阶段可以通过减少尿蛋白,以减轻肾脏损伤,保护肾功能,延缓疾病的进一步发展。

基于AVP-V2R-AQP2通路探讨益气活血方干预慢性心力衰竭水潴留的实验研究

[目的]观察益气活血方对慢性心力衰竭(CHF)大鼠心脏及肾脏结构的影响,并从水的重吸收角度开展机制研究。[方法]对Sprague-Dawley(SD)大鼠进行麻醉处理后,通过左侧冠状动脉前降支结扎方法建立CHF模型。造模4周后,对大鼠进行分组,随机分为假手术组、模型组、卡托普利组及益气活血方低、中、高剂量组。卡托普利组给予卡托普利片13.5 mg/(kg·d),益气活血方各剂量组分别给予益气活血颗粒剂2.5、5、10 g/(kg·d),假手术组及模型组给予等量蒸馏水灌胃,持续灌胃8周。干预结束后采用小动物彩色多普勒超声分析大鼠心脏结构及功能;采集血清检测氨基末端脑利钠肽前体(NT-proBNP)表达水平;采用苏木精-伊红(HE)染色观察大鼠的心肌纤维化水平及肾脏上皮细胞形态;染色后对大鼠肾小管上皮细胞进行分析;通过免疫组织化学方法分析大鼠肾脏水通道蛋白2(AQP2)、pS256-AQP2分布和表达水平;通过酶联免疫吸附(ELISA)法检测血清精氨酸加压素(AVP)水平;通过蛋白免疫印迹(Western Blot)法检测肾脏AQP2、pS256-AQP2、抗利尿激素V2型受体(V2R)表达水平。[结果]与假手术组比较,模型组大鼠射血分数(EF)降低(P<0.01),血清NT-proBNP水平上升(P<0.01);模型组大鼠的心肌形态不规则,出现明显的炎性浸润,肾小管管腔狭窄,模型组AQP2、pS256-AQP2阳性面积高于假手术组,AQP2、AVP、V2R表达上升(P<0.01)。益气活血方各剂量组大鼠EF高于模型组(P<0.01),血清NT-proBNP水平较模型组降低(P<0.01);心肌组织基本保持规则,对应的坏死和凋亡不明显;各给药组大鼠肾小管未见明显异常,肾细胞轻微水肿。卡托普利组、益气活血方中、高剂量组中AQP2、pS256-AQP2阳性表达面积降低(P<0.01或P<0.05),各给药组均能不同程度下调AQP2、pS256-AQP2、AVP、V2R蛋白表达水平。[结论]益气活血方能够通过改善肾脏调节机制,进而调控肾脏对水的重吸收效应,改善心脏结构及功能,延缓CHF进程,其机制可能与调节AVP-V2R-AQP2信号通路的相关因子表达相关。

基于生物信息学和网络药理学探讨补肾健脾方改善2型糖尿病作用机制

目的 基于生物信息学和网络药理学探讨补肾健脾方治疗2型糖尿病(T2DM)的作用机制。方法 通过TCMSP、BATMAN-TCM数据库筛选补肾健脾方活性成分及作用靶点,通过GEO数据库获取T2DM相关数据集GSE18732和GSE19420,通过Mfuzz分析筛选与糖尿病同步变化的基因,作为T2DM疾病靶点。获取补肾健脾方与T2DM疾病靶点交集靶点,作为补肾健脾方治疗T2DM的作用靶点,通过STRING数据库构建靶点蛋白相互作用网络,筛选网络中的关键靶点,通过GO功能和KEGG通路富集分析其生物功能,对关键靶点进行单因素Logistic回归,筛选Hub基因,基于Hub基因构建T2DM预测模型。结果 获取补肾健脾方药物靶点1 837个,T2DM疾病靶点983个,药物-疾病交集靶点115个,主要富集于内分泌抵抗、胰岛素抵抗、胰岛素信号通路、非酒精性脂肪性肝病、细胞凋亡、细胞衰老、AMPK信号通路、糖尿病并发症中的AGE-RAGE信号通路和HIF-1信号通路。Hub基因有NFKB1和SREBF1,预测模型曲线下面积=0.829,具有良好的预测性能。结论 本研究综合生物信息学和网络药理学研究发现,补肾健脾方可能通过调控AMPK通路和AGE-RAGE等通路,发挥延缓T2DM进展作用,但仍需进一步实验验证。

运脾调糖方治疗脾虚湿瘀型2型糖尿病临床研究

目的:探讨运脾调糖方对脾虚湿瘀型2型糖尿病患者糖脂代谢的影响及临床疗效。方法:将120例脾虚湿瘀型2型糖尿病患者分为对照组和观察组各60例。对照组采用甘精胰岛素进行治疗,观察组在对照组的基础上采用运脾调糖方治疗,两组均治疗4周。统计两组治疗后中医证候疗效、糖化血红蛋白(HbA1c)达标率及治疗期间不良反应发生情况,比较两组治疗前后糖代谢指标、动态血糖波动指标、超敏C反应蛋白(hs-CRP)及脂代谢指标水平。结果:治疗后,观察组总有效率93.33%,HbA1c达标率91.67%,对照组总有效率80.00%,HbA1c达标率73.33%,两组比较,差异有统计学意义(P<0.05)。与治疗前比较,治疗后两组血清空腹血糖(FPG)、餐后2 h血糖(2 hPG)、空腹胰岛素(FINS)、HbA1c、平均血糖波动幅度(MAGE)、平均血糖(MBG)、血糖标准差、hs-CRP、甘油三酯(TG)、总胆固醇(TC)及低密度脂蛋白胆固醇(LDL-C)水平均降低(P<0.05),且观察组低于对照组(P<0.05)。治疗期间,观察组和对照组不良反应发生情况比较,差异无统计学意义(P>0.05)。结论:运脾调糖方可有效改善脾虚湿瘀型2型糖尿病患者临床症状及糖脂代谢,降低血糖波动和机体炎症反应。

Effects of Yiqi Yangyin Prescription combined with radiotherapy on the tumor load and anti-tumor immune response of patients with advanced lung cancer

Objective: To investigate the effects of Yiqi Yangyin Prescription combined with radiotherapy on the tumor load and anti-tumor immune response of patients with advanced lung cancer. Methods: A total of 78 patients with advanced non-small cell lung cancer who were diagnosed and treated in our hospital between August 2015 and January 2017 were reviewed and then divided into the routine group (n=41) who received chemoradiotherapy alone and the Yiqi Yangyin Prescription group (n=37) who received chemoradiotherapy combined with Yiqi Yangyin Prescription therapy. The differences in serum levels of tumor markers, Th1/Th2 cytokines and Th17/Treg cytokines were compared between the two groups before and after treatment. Results: After treatment, serum tumor markers CA15-3, Cyfra21-1, HSP90 and CEA levels of Yiqi Yangyin Prescription group were lower than those of routine group;serum Th1 cytokines IFN-γ and IL-2 levels were higher than those of routine group while Th2 cytokines IL-4 and IL-5 levels were lower than those of routine group;serum Th17 cytokines IL-17 and IL-23 as well as Treg cytokines IL-10 and TGF-β levels were lower than those of routine group. Conclusion: Routine chemoradiotherapy combined with Yiqi Yangyin Prescription therapy can effectively reduce the tumor load and optimize the anti-tumor immune function in patients with advanced non-small cell lung cancer.