Thin Layer Identification of Jiedu Shengxue Granules and Determination of Notoginsenoside R1 Content

[Objectives]To establish the quality standard of hospital preparation Jiedu Shengxue granules.[Methods]Scleromitrion diffusum and Prunella vulgaris in Jiedu Shengxue granules were qualitatively identified by thin layer chromatography(TLC).A high performance liquid chromatography(HPLC)was established to determine the content of notoginsenoside R1 in the granule.[Results]The traditional Chinese medicinal materials in Jiedu Shengxue granules could be identified by TLC,and the characteristic spots were stable and clear.Notoginsenoside R1 had a good linear relationship in the range of 10.45-104.5μg/mL,with an average recovery of 98.52%and RSD=2.36%.[Conclusions]TLC and HPLC,as the quality control methods of Jiedu Shengxue granules,have high accuracy and good repeatability,which lays a foundation for the quality control of this mixture.

基于Notch信号通路探讨芪蛭皱肺颗粒对慢性阻塞性肺疾病大鼠Th1/Th2免疫平衡的调节机制

目的探讨果蝇双翅边缘缺刻同源基因(Notch)信号通路在慢性阻塞性肺疾病(COPD)辅助性T细胞1(Helper T cells 1,Th1)和辅助性T细胞2(Helper T cells 2,Th2)失衡中的作用及芪蛭皱肺颗粒的干预机制。方法70只Wistar大鼠随机挑选10只作为空白对照组,其余大鼠均采用香烟烟雾(CS)联合气管滴注脂多糖(Lipopolysaccharide,LPS)法建立COPD模型,空白对照组及造模组各随机挑选3只大鼠验证造模是否成功。造模结束进行灌胃给药干预,造模组大鼠随机分为模型对照组、阳性对照组(67.5μg·kg^(-1))及芪蛭皱肺颗粒高中低剂量组(3.24、1.62、0.81 g·kg^(-1)),分别给予生理盐水、醋酸地塞米松混悬液、芪蛭皱肺高、中、低剂量混悬液进行灌胃干预,空白对照组同模型对照组,灌胃等体积生理盐水。经28天造模及28天治疗后,采用动物肺功能测试系统检测吸气峰流速(Peak Inspiratory Flow,PIF)和呼气峰流速(Peak Expiratory Flow,PEF),处死大鼠提取肺脏、脾脏、血清及支气管肺泡灌洗液(BALF),苏木素-伊红(HE)染色评价肺组织病理变化,酶联免疫吸附实验法(ELISA)测定血清及BALF中肿瘤坏死因子-α(TNF-α)含量,流式细胞仪检测脾脏Th1/Th2细胞水平,免疫组织化学法(Immunohistochemistry,IHC)及蛋白免疫印迹法(Western blot)检测肺组织Notch1、Hes家族发状分裂相关增强子1(Hes1)、Hey家族发状分裂相关增强子1(Hey1)蛋白水平,实时荧光定量聚合酶链式反应(Real-time PCR,RT-PCR)检测肺组织Notch1、Hes1、Hey1基因表达水平。结果与空白对照组比较,模型对照组大鼠肺功能显著降低(P<0.05),肺组织出现炎性细胞浸润、支气管结构破坏等病变,血清及BALF中TNF-α含量显著升高(P<0.05),脾Th1细胞百分比显著降低(P<0.05),Th2细胞百分比显著升高(P<0.05),肺组织Notch1、Hes1、Hey1蛋白及mRNA表达显著升高(P<0.05),差异均具有统计学意义;与模型对照组比较,各给药组大鼠肺功能显著升高(P<0.05),肺组织病理损伤均有所减轻,血清及BALF中TNF-α含量显著降低(P<0.05),脾Th1细胞百分比显著升高(P<0.05),Th2细胞百分比显著降低(P<0.05),肺组织Notch1、Hes1、Hey1蛋白及mRNA表达显著降低(P<0.05),差异均具有统计学意义。结论芪蛭皱肺颗粒通过抑制Notch信号通路调节Th1/Th2平衡,从而改善COPD大鼠肺功能及病理损伤,影响其免疫功能。

Possible mechanisms associated with immune escape and apoptosis on anti-hepatocellular carcinoma effect of Mu Ji Fang granules

BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common digestive system cancers with high mortality rates worldwide.The main ingredients in Mu Ji Fang Granules(MJF)are alkaloids,flavonoids,and polysaccharides.MJF has been used in the clinical treatment of hepatitis,cirrhosis and HCC for more than 30 years.Few previous studies have focused on the mechanism of MJF on tumor immunology in the treatment of HCC.AIM To explore the mechanism of action of MJF on tumor immunology in the treatment of HCC.METHODS The absorbable ingredients of MJF were identified using Molecule Network related to High Performance Liquid Chromatography-Electron Spray Ionization-Time of Flight-Mass Spectrometry,and hub potential anti-HCC targets were screened using network pharmacology and pathway enrichment analysis.Forty male mice were randomly divided into the Blank,Model,and MJF groups(1.8,5.4,and 10.8 g/kg/d)following 7 d of oral administration.Average body weight gain,spleen and thymus indices were calculated,tumor tissues were stained with hematoxylin and eosin,and Interferon gamma(IFN-γ),Tumor necrosis factorα(TNF-α),Interleukin-2,aspartate aminotransferase,alanine aminotransferase,alpha-fetoprotein(AFP),Fas,and FasL were measured by Enzyme-linked Immunosorbent Assay.Relevant mRNA expression of Bax and Bcl2 was evaluated by Real Time Quantitative PCR(RTqPCR)and protein expression of Transforming growth factorβ1(TGF-β1)and Mothers against decapentaplegic homolog(SMAD)4 was assessed by Western blotting.The HepG2 cell line was treated with 10 mg/mL,20 mg/mL,30 mg/mL,40 mg/mL of MJF,and another 3 groups were treated with TGF-β1 inhibitor(LY364947)and different doses of MJF.Relevant mRNA expression of TNF-α,IFN-γ,Bax and Bcl2 was evaluated by RT-qPCR and protein expression of TGF-β1,SMAD2,p-SMAD2,SMAD4,and SMAD7 was assessed by Western blotting.RESULTS It was shown that MJF improved body weight gain and tumor inhibition rate in H22 tumorbearing mice,protected immune organs and liver function,reduced the HCC indicator AFP,affected immunity and apoptosis,and up-regulated the TGF-β1/SMAD signaling pathway,by increasing the relative expression of TGF-β1,SMAD2,p-SMAD2 and SMAD4 and decreasing SMAD7,reducing immune factors TNF-αand IFN-γ,decreasing apoptosis cytokines Fas,FasL and Bcl2/Bax,and inhibiting the effect of LY364947 in HepG2 cells.CONCLUSION MJF inhibits HCC by activating the TGF-β1/SMAD signaling pathway,and affecting immune and apoptotic cytokines,which may be due to MJF adjusting immune escape and apoptosis.

基于SIRT1/PGC-1α信号通路探讨抑眩宁颗粒干预缺血性眩晕的作用机制

目的:探讨抑眩宁颗粒对沉默信息调节因子1(SIRT1)/过氧化物酶体增殖物激活受体γ辅激活因子1α(PGC-1α)信号通路的调控作用及对缺血性眩晕大鼠眩晕症状的改善作用。方法:对清洁级SD大鼠进行电刺激逃避反射训练3 d后建立缺血性眩晕模型。将大鼠分为模型组、抑眩宁颗粒组(6 g/kg)、SIRT1抑制剂(EX527)组(5 mg/kg)、抑眩宁颗粒+EX527组(抑眩宁颗粒6 g/kg+EX5275 mg/kg),各组给予相应药物干预7 d;另取16只清洁级SD大鼠作为假手术组(进行造模前训练,仅穿线不结扎)。采用跳台逃避实验测定跳台逃避潜伏期;多普勒激光血流仪测量大鼠前庭神经核组织血流量,计算血流量下降率;苏木精-伊红染色观察大鼠脑组织病理特征;酶联免疫吸附法检测大鼠脑组织丙二醛(MDA)、超氧化物歧化酶(SOD)活性、一氧化氮(NO)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)含量;蛋白免疫印迹法检测大鼠脑组织SIRT1、PGC-1α、B淋巴细胞瘤-2相关X蛋白(Bax)、B淋巴细胞瘤-2(Bcl-2)蛋白表达水平。结果:与假手术组比较,模型组大鼠脑组织神经细胞变形、固缩和凋亡,跳台逃避潜伏期、给药后血流量下降率、脑组织MDA、NO、IL-1β、TNF-α含量、Bax蛋白表达水平升高(P<0.05),SOD活性、SIRT1、PGC-1α和Bcl-2蛋白表达水平降低(P<0.05)。与模型组比较,抑眩宁颗粒组大鼠脑组织凋亡变异的细胞数量减少,胶质周围的正常细胞数量增多,跳台逃避潜伏期、给药后血流量下降率、脑组织MDA、NO、IL-1β、TNF-α含量及Bax蛋白表达水平降低(P<0.05),SOD活性、SIRT1、PGC-1α和Bcl-2蛋白表达水平升高(P<0.05);EX527组大鼠脑组织神经细胞严重变形,固缩和凋亡现象明显,跳台逃避潜伏期、给药后血流量下降率、脑组织MDA、NO、IL-1β、TNF-α含量及Bax蛋白表达水平升高(P<0.05),SOD活性、SIRT1、PGC-1α和Bcl-2蛋白表达水平降低(P<0.05)。EX527可逆转抑眩宁颗粒对缺血性眩晕大鼠的改善作用(P<0.05)。结论:抑眩宁颗粒可能通过激活SIRT1/PGC-1α通路、抑制氧化应激和炎症反应,进而改善缺血性眩晕大鼠眩晕症状。

槐耳颗粒通过抑制Bmi-1与CD133表达减少三阴性乳腺癌全身转移的研究

目的研究在不同给药方式下槐耳颗粒对三阴性乳腺癌细胞的作用效果,及槐耳颗粒是否可以影响Bmi-1进而调节肿瘤细胞CD133表达以发挥抑制肿瘤细胞转移的作用。方法选择40只3~4周龄雌性裸鼠随机分成四组,预防组、预防及治疗组、治疗组分别于建模前3周、建模前及建模后3周、建模后3周口服给予槐耳清膏溶液,对照组不给予药物治疗;建模方式采用左心室注射的方法建立三阴性乳腺癌全身转移模型,建模后六周观察期后统一处死裸鼠并取标本;通过Kaplan-Meier法分析裸鼠生存时间,免疫组化法检测裸鼠转移灶内CD133及Bmi-1的表达,组间比较采用方差分析。结果预防及治疗组裸鼠的生存时间最长(MST=42d),其次为治疗组(MST=39d),再次为预防组(MST=38 d),对照组裸鼠的生存时间最短(MST=32d);预防及治疗组的Bmi-1平均表达最低,对照组的Bmi-1平均表达最高,不同给药方式与Bmi-1的表达之间存在显著性差异(P<0.05);预防及治疗组的CD133平均表达最低,对照组的CD133平均表达最高,不同给药方式与CD133的表达之间存在显著性差异(P<0.05)。结论槐耳颗粒对三阴性乳腺癌全身转移具有预防及治疗作用;槐耳颗粒可能通过激活Bmi-1凋亡基因从而减少了三阴性乳腺癌干细胞CD133的比例,进而发挥了预防及治疗三阴性乳腺癌全身转移的作用。

运脾消食颗粒对厌食模型幼龄大鼠下丘脑、胃窦及十二指肠β-EP、nesfatin-1影响研究

目的研究厌食模型幼龄大鼠下丘脑、胃窦、十二指肠中β-内啡肽(β-EP)、新型神经肽-1(nesfatin-1)的含量及蛋白表达情况,以及中药复方运脾消食颗粒对两者的干预作用。方法选取SPF级72只Wistar幼龄大鼠,雌雄各半,日龄30 d,体质量(60±10)g,随机分为空白组(12只)和造模组(60只),造模组以病因和症状模型法建立幼龄大鼠厌食症模型。造模成功后的动物随机分为模型组、阳性组(儿宝颗粒组)、运脾消食颗粒高剂量组、运脾消食颗粒中剂量组、运脾消食颗粒低剂量组,每组12只,空白组和模型组灌胃等量0.9%氯化钠溶液,其余4组分别给予等体积的儿宝颗粒混悬液(1.75 g/kg)、运脾消食颗粒高剂量混悬液(4.20 g/kg)、运脾消食颗粒中剂量混悬液(2.10 g/kg)、运脾消食颗粒低剂量混悬液(1.05 g/kg),连续给药14 d,最后一次给药结束禁食禁水24 h后,采集标本,用ELISA法和Western Blot法分别检测大鼠下丘脑、胃窦、十二指肠中β-EP、nesfatin-1的含量和蛋白表达。结果①模型组大鼠下丘脑、胃窦、十二指肠β-EP含量及蛋白表达降低,治疗后儿宝颗粒组大鼠下丘脑、胃窦、十二指肠β-EP含量及蛋白表达增加,运脾消食颗粒高、中剂量组大鼠下丘脑、胃窦、十二指肠β-EP含量及蛋白表达增加;②模型组大鼠下丘脑、胃窦、十二指肠nesfatin-1含量及蛋白表达增加,治疗后儿宝颗粒组大鼠下丘脑、胃窦、十二指肠nesfatin-1含量及蛋白表达降低,运脾消食颗粒高、中剂量组大鼠下丘脑、胃窦、十二指肠nesfatin-1含量及蛋白表达降低。结论运脾消食颗粒可显著降低下丘脑、胃窦、十二指肠中nesfatin-1含量及蛋白表达水平,而增加下丘脑、胃窦、十二指肠中β-EP含量及蛋白水平;可改善模型大鼠的胃肠功能,调节脑肠肽水平,增加食欲,这可能是运脾消食颗粒治疗小儿厌食症的重要机制之一。

胃苏颗粒联合泮托拉唑对非萎缩性胃炎患者胃肠激素及血清MCP-1、EGF的影响

目的探讨胃苏颗粒联合泮托拉唑对非萎缩性胃炎患者胃肠激素及血清单核细胞趋化因子-1(MCP-1)、表皮生长因子(EGF)的影响。方法选取2020年1月~2023年1月在我院就诊的非萎缩性胃炎患者116例,按照随机数字表法分为观察组和对照组,每组58例。对照组给予泮托拉唑20mg,2次/d,连续4周;观察组在对照组基础上加用胃苏颗粒5g,3次/d,连续4周。比较两组患者治疗前后胃肠激素(胃泌素、胆囊收缩素、生长抑素、血清素)及血清MCP-1、EGF的水平变化,以及临床疗效和不良反应。结果治疗后,两组患者的胃泌素和生长抑素水平明显升高,胆囊收缩素和血清素水平明显降低(P<0.001);血清MCP-1水平明显降低、EGF水平明显升高,两组相比差异有统计学意义(P=0.007、0.008)。治疗后观察组的临床症状总分低于对照组(P<0.001)。观察组的总有效率为93.10%,显著高于对照组(74.14%),差异有统计学意义(P=0.009)。两组患者均未出现严重不良反应。结论胃苏颗粒联合泮托拉唑能够有效调节非萎缩性胃炎患者的胃肠激素及血清MCP-1、EGF水平,改善胃黏膜的修复和保护功能,提高临床疗效,安全性好。

Research on the effect of Huangqi and Zeling granule combined with Zhushui No.1 paste on patients with cirrhosis

OBJECTIVE: To explore the clinical effect of Huangqi and Zeling granule combined with Zhushui No.l paste plus conventional therapy on patients with cirrhosi.METHODS: Totally 90 patients with liver cirrhosis were randomly assigned into two groups: control group and study group. They all met the inclusion criteria. The patients in the control group were treated by conventional treatment; the patients in the study group received Huangqi and Zeling granule and Zhushui No. 1 paste along with the conventional therapy.The paste was applied on the acupoint of shenque. The levels of LPS, ET-1, NO and AM ON were all measured before and after treatment. The depth of ascites, the change of diameter portal and size of spleen were performed by abdominal ultrasonography Adverse events were observed and documented.RESULTS: The levels of AMON, LPS, ET-1 and NO were all reduced after treatment which were more obviously in study group(P<0.05). The depth decreased in both study group and control group after treatment. However, the decrease was more in the study group than in the control group(P<0.05).CONCLUSION: The effect of Huangqi and Zeling granule plus Zhushui No. 1 paste combined with routine conventional therapy on cirrhosis was better than that of using the routine conventional therapy alone.

基于Nrf2/HO-1通路探讨健骨颗粒含药血清对氧化应激状态成骨细胞骨形成的调控机制

目的 基于Nrf2/HO-1通路探讨健骨颗粒含药血清对氧化应激状态成骨细胞骨形成的调控机制。方法 取6周龄SPF级雄性SD大鼠40只,随机分为健骨颗粒组和生理盐水组各20只。健骨颗粒组每天灌服含生药量7.8 g/kg健骨颗粒浸膏稀释液2 mL,生理盐水组每天灌服生理盐水2 mL,2组每日灌胃1次,灌胃7 d后取大鼠腹主动脉血制备健骨颗粒含药血清和生理盐水血清。将课题组前期选用UMR-106细胞构建的Nrf2敲减稳定株细胞和Nrf2阴性对照细胞,分别分为Nrf2-KD+JG组、Nrf2-KD+NS组和NC+JG组、NC+NS组。Nrf2-KD+JG组和NC+JG组分别采用10%健骨颗粒含药血清加高糖DMEM培养12 h;Nrf2-KD+NS组和NC+NS组分别采用10%生理盐水血清加高糖DMEM培养12 h,再用10μmol/L过氧化氢干预12 h;采用超氧化物阴离子荧光探针(DHE)检测4组超氧化物阴离子含量,茜素红染色实验观察4组矿化结节数量,Western blot检测4组Nrf2、核Nrf2、HO-1、RUNX2蛋白相对表达量。结果 与NC+JG组比较,Nrf2-KD+JG组超氧化物阴离子含量增多(P<0.05),显微镜下可见矿化结节数量减少,Nrf2、核Nrf2、HO-1和RUNX2蛋白相对表达量均明显降低(P<0.05)。与NC+NS组比较,Nrf2-KD+NS组超氧化物阴离子含量增多,显微镜下可见矿化结节数量减少,4个指标蛋白相对表达量均明显降低(P<0.05),NC+JG组超氧化物阴离子含量显著降低(P<0.05),显微镜下可见矿化结节数量增多,4个指标蛋白相对表达量均明显升高(P<0.05)。结论 健骨颗粒可以激活成骨细胞内Nrf2/HO-1信号通路,降低细胞内氧化应激水平,增强细胞矿化能力,促进成骨细胞骨形成。

养肝益水颗粒对SHR大鼠血压及ET-1、NO的影响

目的通过对自发性高血压大鼠(SHR)血压、循环及肾脏组织内皮素(ET-1)、一氧化氮(NO)浓度的检测,观察养肝益水颗粒对SHR大鼠肾脏保护作用。方法将SHR大鼠随机分为养肝益水颗粒治疗组(以下简称养肝益水组)、卡托普利治疗组(以下简称卡托普利组)、模型对照组,每组均8只,Wistar-Kyoto(WKY)大鼠8只作为正常对照组。灌胃6周后处死,检测其血压、循环及肾脏组织内ET-1及NO的浓度。结果养肝益水颗粒能降低SHR大鼠血压进行性增高的趋势;治疗后养肝益水组循环ET-1浓度略有下降,但与模型对照组比较无明显差异(P>0.05);治疗后养肝益水组肾脏组织ET-1浓度较模型对照组有显著下降,其差异有统计学意义(P<0.01);治疗后养肝益水组循环NO浓度略有升高,但与模型对照组比较无明显差异(P>0.05),与正常对照组比较其差异有统计学意义(P<0.05);治疗后养肝益水组肾脏组织NO浓度较模型对照组有显著升高,其差异有统计学意义(P<0.01)。结论养肝益水颗粒能持久降低SHR大鼠血压,降低SHR大鼠肾脏组织ET-1浓度;升高SHR大鼠肾脏组织NO浓度,从而起到保护肾脏的作用。

健足颗粒对糖尿病皮肤溃疡大鼠血清NO ET-1水平的影响

目的:观察健足颗粒(加减防己黄芪汤)对糖尿病皮肤溃疡大鼠血管内皮功能的影响。方法:选用SD雄性大鼠90只,随机选取6只为正常对照组,其余大鼠以尾静脉注射四氧嘧啶40mg/kg,筛取符合糖尿病诊断标准的大鼠用于建立糖尿病皮肤溃疡模型,并随机分成6组,模型对照组、健足颗粒干预的高、中、低剂量组,中药对照组、西药对照组。实验结束后断头取血检测NO、ET-1含量以观察健足颗粒对血管内皮功能的影响。结果:与模型组比较,各治疗组大鼠血清NO含量均有不同程度升高,而血浆ET-1含量却有不同程度的降低,其中以健足颗粒高剂量组变化最明显(P<0.001),其次为中剂量(P<0.01),低剂量、中药对照组次之(P<0.05),西药对照组也有轻度改变,但无显著统计学意义(P>0.05)。健足颗粒各剂量组的调节作用与剂量呈现相关性。结论:健足颗粒可通过升高血清NO含量、降低血浆ET-1水平来改善血管内皮功能,有效防治糖尿病皮肤溃疡发生发展。

益肺活血颗粒对老年肺心病患者ET-1、NO的影响

目的观察益肺活血颗粒对老年慢性肺源性心脏病(CPHD)患者血管内皮素-1(ET-1)、一氧化氮(NO)的影响。方法选择108例符合中西医诊断标准的老年CPHD患者,随机分为益肺活血颗粒治疗组56例,对照组52例,治疗14 d后,观察2组临床疗效,评价氧分压(PaO2)、二氧化碳分压(PaCO2)及ET-1、NO水平。结果治疗组总有效率为92.86%,优于对照组78.85%(P<0.05);治疗组与对照组PaO2、PaCO2及ET-1、NO指标均较治疗前改善,但治疗组较对照组提高PaO2、降低PaCO2更明显,降低ET-1、提高NO水平更显著,差异有统计学意义(P<0.05),且药物治疗安全性好。结论益肺活血颗粒能有效治疗老年CPHD,降低ET-1、提高NO水平。

仙花活骨丹颗粒对实验性股骨头缺血性坏死大鼠血清ET-1、NO和VEGF的影响

目的:观察仙花活骨丹颗粒对实验性股骨头缺血性坏死大鼠血清内皮素(ET-1)、一氧化氮(NO)和血管内皮生长因子(VEGF)水平的影响。方法:采用仙花活骨丹颗粒对实验性股骨头缺血性坏死大鼠进行不同剂量的药剂治疗,并与正常组、模型组和仙灵骨葆组进行比较,采用酶联免疫吸附试验(ELISA)测定大鼠血清中ET-1、VEGF含量,硝酸还原酶法测定NO含量。结果:①与正常组比较,模型组大鼠血清NO含量明显偏低。与模型组比较,各治疗组大鼠血清NO含量均有不同程度升高,其中仙花活骨丹颗粒大剂量组升高最明显(P<0.001),中剂量组较明显(P<0.01),小剂量组、仙灵骨葆组次之(P<0.05)。②与正常组比较,模型组大鼠血清ET-1含量明显偏高。与模型组比较,各治疗组大鼠血清ET-1含量均有不同程度降低,其中仙花活骨丹颗粒大剂量组降低最明显(P<0.001),中剂量组较明显(P<0.01),小剂量组、仙灵骨葆组次之(P<0.05)。③与正常组比较,模型组大鼠血清VEGF含量明显偏低。与模型组比较,仙花活骨丹颗粒大剂量组升高最明显(P<0.001),中剂量组较明显(P<0.01),小剂量组、仙灵骨葆组也略微升高,但无统计学意义(P>0.05)。结论:仙花活骨丹颗粒能促进毛细血管的再生与修复,改善病变股骨头的血运,加速坏死股骨头的修复过程,从而发挥良好的防治作用。

金果胃康颗粒对实验性胃黏膜损伤大鼠血浆ET-1、NO的影响

目的:观察研究中药复方金果胃康颗粒抗胃黏膜损伤的作用及其机理。方法:50只SD系大鼠,随机分为5组:A(空白对照组)、B(模型对照组)、C(丽珠得乐组)、D(金果胃康大剂量组)、E(金果胃康小剂量组)。除空白对照组外,给大鼠灌服无水乙醇造成胃黏膜损伤模型,造模前先灌服金果胃康,观察金果胃康对黏膜损伤的影响,并测定血浆一氧化氮(NO)和内皮素(ET1)水平。结果:经金果胃康处理后,乙醇对大鼠的胃黏膜损伤明显减轻,损伤指数显著降低(P<0.01);血浆ET1水平降低(P<0.01),NO水平升高(P<0.01),ET/NO平衡受到破坏。结论:金果胃康颗粒具有保护胃黏膜的作用,其机理可能与影响体内ET1、NO水平,ET1、NO平衡失调有关。

枫蓼肠胃康颗粒对肥胖诱导2型糖尿病大鼠糖脂代谢及GLP-1的影响

目的 探讨枫蓼肠胃康颗粒对肥胖诱导的2型糖尿病大鼠糖脂代谢及胰高血糖素样肽-1(GLP-1)的影响。方法 7周龄SD大鼠70只,随机取10只作为分为空白组,给予正常饲料喂养;其余大鼠采用高脂高糖饲料喂养结合腹腔注射链脲佐菌素方法建立2型糖尿病模型。将造模成功2型糖尿病大鼠随机分为模型组、西格列汀组及枫蓼肠胃康低、中、高剂量组,每组10只。西格列汀组给予西格列汀16.7 mg/kg灌胃,枫蓼肠胃康低、中、高剂量组分别给予2.65 g/kg、5.3 g/kg、10.6 g/kg枫蓼肠胃康颗粒灌胃,空白组和模型组给予生理盐水灌胃,均1次/d,连续4周。测量各组大鼠造模结束和灌胃4周后体重,检测各组大鼠灌胃4周后血糖、血清胰岛素、血脂[胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)]及血清GLP-1水平,免疫组织化学法检测回肠组织中GLP-1表达情况。结果 灌胃4周后,枫蓼肠胃康中、高剂量组及西格列汀组大鼠体重与造模后比较差异无统计学意义(P均>0.05);模型组与枫蓼肠胃康低剂量组大鼠体重与造模后比较均明显降低(P均<0.05)。枫蓼肠胃康中、高剂量组和西格列汀组大鼠空腹血糖、负荷后30 min血糖、负荷后60 min血糖、负荷后120 min血糖和空腹胰岛素水平均明显低于模型组(P均<0.05);枫蓼肠胃康高剂量组和西格列汀组大鼠负荷后60 min和120 min血糖均明显低于枫蓼肠胃康低剂量组(P均<0.05);枫蓼肠胃康中剂量组和西格列汀组大鼠负荷后60 min胰岛素水平均明显高于枫蓼肠胃康低剂量组(P均<0.05)。枫蓼肠胃康高剂量组和西格列汀组大鼠血清TC、TG、LDL-C水平及枫蓼肠胃康中剂量组大鼠血清TC、TG水平均明显低于模型组(P均<0.05),枫蓼肠胃康中剂量组大鼠HDL-C水平明显高于模型组(P均<0.05)。枫蓼肠胃康中、高剂量组和西格列汀组血清GLP-1水平均明显高于模型组(P均<0.05),枫蓼肠胃康高剂量组和西格列汀组均明显高于枫蓼肠胃康低剂量组(P均<0.05)。枫蓼肠胃康颗粒中、高剂量组和西格列汀组大鼠回肠组织中GLP-1平均光密度值均明显高于模型组(P均<0.05)。结论 枫蓼肠胃康颗粒能够降低肥胖诱导的2型糖尿病大鼠血糖,改善血脂代谢,机制可能与其调节肠道分泌GLP-1功能有关。

复方地黄颗粒对帕金森病阴虚动风证大鼠纹状体GLAST、GLT-1及GAT-1表达的影响

目的观察复方地黄颗粒对帕金森病(PD)阴虚动风证大鼠纹状体谷氨酸/天冬氨酸转运体(GLAST)、谷氨酸转运体1(GLT-1)、γ-氨基丁酸转运体1(GAT-1)表达的影响,探讨其潜在作用机制。方法采用6-羟基多巴胺注射损伤黑质法制备PD阴虚动风证大鼠模型,将成模大鼠随机分为模型组、美多芭组(150 mg/kg)和复方地黄颗粒低、中、高剂量组(1.75、3.5、7 g/kg),每组11只,另取11只作为正常对照组、11只作为假手术组。正常对照组、假手术组及模型组予生理盐水灌胃,美多芭组及复方地黄颗粒各剂量组灌胃相应药物,连续28 d。观察大鼠神经行为学变化,RT-qPCR、Western blot及免疫组化检测损伤侧纹状体GLAST、GLT-1和GAT-1表达。结果与正常对照组和假手术组比较,模型组大鼠神经行为学实验旋转圈数增加,悬挂时间及移动格数减少(P<0.01),损伤侧纹状体GLAST、GLT-1 mRNA和蛋白表达降低,GAT-1 mRNA和蛋白表达升高(P<0.01);与模型组比较,美多芭及复方地黄颗粒各剂量组大鼠神经行为学实验旋转圈数减少,悬挂时间及移动格数增加(P<0.01),损伤侧纹状体GLAST、GLT-1 mRNA和蛋白表达升高,GAT-1 mRNA和蛋白表达降低(P<0.05,P<0.01),以复方地黄颗粒高剂量组作用最明显(P<0.05,P<0.01),与美多芭组差异无统计学意义(P>0.05)。结论复方地黄颗粒可能通过上调GLAST、GLT-1及下调GAT-1水平,改善谷氨酸与γ-氨基丁酸失衡,发挥治疗PD阴虚动风证作用。

Pharmacological evaluation and mechanistic study of compound Xishu Granule in hepatocellular carcinoma

Objective:In this study,we used HepG2 human hepatocellular carcinoma cells to study the effects of Compound Xishu Granule(CXG)on cell proliferation,apoptosis,and the cell cycle in vitro.We also used a xenograft tumor model to study the anti-tumor effects of CXG and related mechanisms in vivo.Methods:The effect of CXG on cell viability was measured using Cell Counting Kit-8 and a colony formation assay.The effect of CXG on apoptosis and the cell cycle was analyzed using flow cytometry.The in vivo anti-tumor effect of CXG was assessed by measuring the volume change in xenograft tumors after drug administration.The CXG anti-tumor mechanism was studied using western blotting assay to detect cell cycle and apoptotic associated proteins.Results:CXG suppressed HepG2 cell proliferation in a time-and dose-dependent manner in vitro.Colony formation experiments showed that CXG administration for 24 h significantly reduced HepG2 cell formations(P<.01).Flow cytometric analysis showed that CXG treatment for 48 h promoted apoptosis and blocked HepG2 cells in the G2/M phase.Western blotting results showed that Bax was significantly upregulated and Bcl-2 was down-regulated in graft tumor tissues and HepG2 cells after CXG administration,which increased the Bax/Bcl-2 ratio.PLK1,CDC25 C,CDK1,and Cyclin B1 expression were upregulated.CXG had a good inhibitory effect on graft tumor growth in vivo.Conclusion:CXG has good anti-tumor effects in vitro and in vivo.In vitro,CXG promoted HepG2 cell apoptosis and induced G2/M phase arrest.In vivo,CXG significantly inhibited graft tumor growth.The CXG mechanism in treating hepatocellular carcinoma may be that CXG can induce abnormal apoptotic and cell cycle associated protein expression,leading to mitotic catastrophe and apoptosis.

Paclitaxel-induced stress granules increase LINE-1 mRNA stability to promote drug resistance in breast cancer cells

Abnormal expression of long interspersed element-1(LINE-1)has been implicated in drug resistance,while our previous study showed that chemotherapy drug paclitaxel(PTX)increased LINE-1 level with unknown mechanism.Bioinformatics analysis suggested the regulation of LINE-1 mRNA by drug-induced stress granules(SGs).This study aimed to explore whether and how SGs are involved in drug-induced LINE-1 increase and thereby promotes drug resistance of triple negative breast cancer(TNBC)cells.We demonstrated that SGs increased LINE-1 expression by recruiting and stabilizing LINE-1 mRNA under drug stress,thereby adapting TNBC cells to chemotherapy drugs.Moreover,LINE-1 inhibitor efavirenz(EFV)could inhibit drug-induced SG to destabilize LINE-1.Our study provides the first evidence of the regulation of LINE-1 by SGs that could be an important survival mechanism for cancer cells exposed to chemotherapy drugs.The findings provide a useful clue for developing new chemotherapeutic strategies against TNBCs.

Effect of Qi Kwai Granule particles on expression of TGF-β1 and MCP-1 in kidney of diabetic nephropathy rats

OBJECTIVE To observe the effect of Qi Kwai Granule particles on the expression of in.terleukin 6(IL-6),monocyte chemotactic protein 1(MCP-1) and transforming growth factor-β1(TGF-β1)in diabetic nephropathy(DN) rats and evaluate the protective effect of Qi Kwai Granule particles against renal injury of diabetic nephropathy.METHODS This experiment adopts adopted the high-sugar-highfat diet and intraperitoneal injection of 2% STZ+ unilateral renal ligation to establish rat model of diabet.ic nephropathy.50 model rats were then randomly divided into model group,Irbesartan group,Qi Kwai Granule particles of high,medium,low dose group,10 rats in each group.10 normal rats were set as the sham operation group.Intragastric administration for 8 weeks were measured in rats.Measure the value of rat blood glucose by blood glucose meter,the determination of serum interleukin 6(IL-6) con.tent by ELISA,the expression of MCP-1 and TGF-β1 by immunohistochemistry method.The value of rat blood glucose were measured by blood glucose meter.Serum interleukin 6(IL-6) were determinat.ed by ELISA.Expression of MCP-1 and TGF-β1 were evaluated by immunohistochemistry method.RE.SULTS The blood glucose of Qi Kwai Granule particles of high,medium groups were decreased com.pared with those of the model group(P<0.05).The content of IL-6 of Qi Kwai Granule particles of high,medium groups were reduced(P<0.01).The content of MCP-1,TGF-β1 in kidney of Qi Kwai Granule particles of high,medium,low dose groups were decreased(P<0.01).CONCLUSION Qi Kwai parti.cles have protective effect on renal tissue of diabetic nephropathy rats.Its mechanism might be related to the decrease of blood glucose value and IL-6,the inhibition of the expression of MCP-1 and TGF-β1.

Use of network pharmacology and molecular docking to explore the potential mechanism governing the efficacy of Jinhuaqinggan granules in the treatment of novel coronavirus-induced pneumonia

Background:Now that the epidemic of new coronavirus pneumonia(corona virus disease 2019)is spreading all over the world,Jinhuaqinggan granules in the Chinese treatment plan has been proved to be an effective Chinese patent medicine for the treatment of corona virus disease 2019.Methods:This study aims to clarify the possible therapeutic mechanism governing the efficacy of Jinhuaqinggan granules in the treatment of corona virus disease 2019,through using network pharmacology and molecular docking.During the analysis,227 active components were obtained and screened by using the ADME method.Furthermore,282 Jinhuaqinggan granule targets and 56 common targets with corona virus disease 2019 were gathered from various databases.Then the protein-protein interaction network of Jinhuaqinggan granules and corona virus disease 2019 targets were constructed and 6 core targets were selected through network topology analysis.In addition,A total of 262 biological function annotation entries(P<0.01)and 101 pathways(P<0.01)were obtained by gene ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis.Results:Molecular docking showed that quercetin,luteolin,kaempferol,wogonin and naringin had an affinity for SARS-CoV-23CL hydrolase and angiotensin-converting enzyme 2.Conclusion:corona virus disease 2019 can be prevented by the primary targets of Jinhuaqinggan granules.The most important bioactive components in Jinhuaqinggan granules-quercetin,naringenin,luteolin and wogonin-can play antiviral effect,anti-inflammatory storm,regulate immunity by regulating signal transducers and activators of transcription 1,interleukin 4,interferon-γ,heme oxygenase 1 and acting on the lipopolysaccharide response,toll-like receptor signaling pathway,mitogen-activated protein kinase signaling pathway,etc.