黄连素联合培菲康治疗腹泻型肠易激综合征的临床疗效观察

目的:观察黄连素联合培菲康治疗腹泻型肠易激惹综合征的疗效和安全性。方法:将90例腹泻型肠易激惹综合征患者分为三组,每组病例均30例。联合治疗组为黄连素联合培菲康治疗组;对照组两组为单用培菲康组和单用黄连素组。治疗2周后三组进行疗效比较。结果:联合治疗组总有效率93.3%,单用黄连素组总有效率66.7%,单用培菲康组总有效率70.0%,联合治疗组总有效率明显优于各单用药物对照组(P<0.05),单用黄连素组与单用培菲康组比较,总有效率差异无显著性(P>0.05)。三组患者均未发现明显的不良反应。结论:黄连素联合培菲康治疗腹泻型肠易激综合征安全、有效,值得临床推广使用。     

黄连素联合阿托伐他汀对急性脑梗死患者治疗作用的研究

目的：探讨黄连素联合阿托伐他汀对急性脑梗死（ACI）患者血清炎症因子（MIF、IL-6、CRP）水平及短期临床预后的作用。方法：选择120例ACI患者,随机分为联合组（n=60）和阿托伐他汀组（n=60）。两组均给予ACI常规治疗。联合组给予黄连素（300 mg tid）+阿托伐他汀（40 mg qd）,阿托伐他汀组仅给予阿托伐他汀（40 mg qd）。测定所有患者的血清MIF、IL-6、CRP水平（入院第1、14天）及进行神经功能缺损评分（入院第1、14、90天）。结果：入院第1天及第14天,两组患者血清MIF、IL-6、CRP水平与NIHSS评分呈正相关（P<0.05）;入院第1天,两组间患者的MIF、IL-6、CRP水平及NIHSS评分比较均无统计学意义（P>0.05）;入院第14天较第1天,两组患者的血清MIF、IL-6、CRP水平及NIHSS评分均显著降低（P<0.05）;入院第14天,联合组较阿托伐他汀组血清MIF、IL-6、CRP水平及NIHSS评分显著降低（P<0.05）;随访第90天,联合组较阿托伐他汀组mRS评分显著偏低（P<0.05）,短期预后良好率显著偏高（P<0.05）。结论：对急性脑梗死的治疗,黄连素联合阿托伐他汀治疗可显著降低ACI急性期血清炎症因子MIF、IL-6、CRP水平,并显著促进神经功能恢复,改善短期预后。     

滋阴丸中盐酸小檗碱和芒果苷提取工艺的考察

目的探究采用高效液相法测定中药复方滋阴丸中盐酸小檗碱和芒果苷的含量并优化其提取工艺。方法以水作为提取溶剂,通过正交实验,以高效液相色谱法测定盐酸小檗碱和芒果苷的含量为指标,考察提取溶剂体积、提取时间以及提取次数对提取效果的影响,优选出最佳的提取工艺。结果用标准曲线法定量得盐酸小檗碱和芒果苷的平均加样回收率分别为99.2%和101.2%,相对标准偏差RSD为1.5%和2.2%。由正交试验可得滋阴丸复方经9种提取工艺提取后,以芒果苷和盐酸小檗碱为指标进行评价,15倍水溶解,提取2次,每次1 h,可以达到最佳的提取效果。结论此法简便、迅速、准确,不经分离可直接测定中药复方滋阴丸中盐酸小檗碱和芒果苷的含量,且结果可靠,稳定性好,回收率高,为中药分析提供一种可靠的方法。     

Pre-clinical toxicity of a combination of berberine and 5-aminosalicylic acid in mice

Our previous study demonstrated that a combination of alternative medicine berberine and conventional 5-aminosalicylic acid (5-ASA) showed promise to be a novel therapeutic strategy for ulcerative colitis (UC). This present study aims to sketch the pre-clinical toxicity profile of this combination (1:10 dose ratio) on mice. In acute toxicity test, the determined median lethal dose (LD₅₀) was 278.7 mg/kg berberine plus 2787 mg/kg 5-ASA. The results from subacute toxicity test demonstrated that no toxic signs of clinical symptoms, no significant changes in hematological or biochemical parameters were detected in mice treated with 14 + 140, 28 + 280 or 56 + 560 mg/kg of berberine plus 5-ASA treatment. Histological examinations revealed that accompanied with an increase in spleen weight, frequently recorded enlargement and white pulp hyperplasia of spleen were detected in mice when exposed to three doses of combination treatments. Further in vitro assessment suggested that the spleen toxicity was originated from berberine by its inhibition in cell viability and cell proliferation of lymphocytes. The results of this study indicate that the combination of berberine and 5-ASA shows a slight toxic effect on spleen, suggesting that this combination should be used with caution for patients.     

Berberine inhibits SDF-1-induced AML cells and leukemic stem cells migration via regulation of SDF-1 level in bone marrow stromal cells

Berberine plays a prominent role on the control of tumor cell invasion and migration. SDF-1 is a homeostatic chemokine that signals through CXCR4 which is expressed by hematopoietic tumor cells. The SDF-1/CXCR4 axis is involved in the migration process of leukemic cells. In this study, we investigated the effects of berberine on the SDF-1-induced HL-60 cells, primary acute myeloid leukemia (AML) cells and leukemic stem cells (LSCs) migration. Transwell migration chambers (8 μm) were used to assess the role of berberine on leukemic cell migration; Flow cytometry was used to analyze the role of berberine on the CXCR4 expression; SDF-1 protein level secreted by bone marrow stromal cells (BMSCs) was evaluated by ELISA. Results demonstrated that berberine could partly inhibit SDF-1-induced AML cells as well as LSCs migration. Berberine could reduce SDF-1 protein level secreted by BMSCs in the microenvironment but not affect CXCR4 expression on HL-60 cell membrane, and we hypothesized that berberine could inhibit AML cells migration partly by reducing the secreting of SDF-1 by BMSCs and inhibiting HERG1 K⁺ channels of leukemic cells. Therefore, it is speculated that berberine might be a potentially effective agent for prevention of leukemia.     

小檗碱对HepG2细胞肝细胞核因子基因表达的影响

[目的]观察小檗碱对人肿瘤细胞株(HepG2)细胞肝细胞核因子(HNF1α、HNF1β、HNF4α、HNF6)mR-NA表达和糖代谢相关激酶作用的影响,探讨小檗碱治疗糖尿病的分子机制。[方法]对不同浓度小檗碱(0、0.1、0.3、1、3、10、30μmol/L)和1 mmol/L二甲双胍处理24 h后的HepG2细胞,采用RT-PCR方法检测其HNFs mR-NA表达,同时检测糖代谢相关激酶(葡萄糖激酶、L-丙酮酸激酶、磷酸烯醇式丙酮酸激酶)活性。[结果]与对照组比较,小檗碱能够一定程度下调HepG2细胞HNFs mRNA表达,调节肝脏葡萄糖代谢相关激酶活性。[结论]小檗碱下调HepG2细胞HNFs mRNA表达,调节肝脏葡萄糖代谢相关激酶活性,这可能是其治疗糖尿病的机制之一。     

黄连素对慢性心力衰竭患者心功能和血管内皮细胞功能的影响

目的观察黄连素对慢性心力衰竭（心衰）患者心功能、血管内皮细胞功能的影响。方法人选65例慢性心衰患者，根据纽约心脏病协会（NYHA）分级标准进行心功能分级，比色法测一氧化氮（NO），ELISA法检测N末端脑钠素原（NT～PmBNP），超声心动图测左室射血分数（LVEF），并与健康对照组30例进行比较。心衰患者随机分为常规组和黄连素组，2个月后复查。结果心衰心功能Ⅲ级、Ⅳ级组与对照组比较，血NO及LVEF差异有统计学意义（P均〈O．01）；LN（NT—Pr0BNP）在对照组与心衰各心功能分级间差异均有统计学意义（P均〈O．05）。2个月治疗后，黄连素组心功能明显改善，黄连素组较常规组LVEF明显增加，LN（NT—proBNP）及血NO明显降低（P均〈0．05）。结论血管内皮细胞功能及LN（NT～ProBNP）与心衰严重程度有关。黄连素可明显改善慢性心衰患者心功能，与血管内皮细胞功能改善有关。     

小檗碱对家兔颈动脉粥样硬化组织核因子кB、血管细胞粘附分子1及单核细胞趋化蛋白1表达的影响

目的探讨小檗碱预防家兔颈动脉粥样硬化形成的作用机制。方法将24只大白兔随机分为正常对照组、模型组和小檗碱组。正常对照组给予普通饮食,模型组和小檗碱组给予高脂饲料喂养1周后行右侧颈动脉内膜空气干燥术,术后继续高脂饲料喂养4周以制成颈动脉粥样硬化模型,小檗碱组在给予高脂饲料喂养的同时每日灌服小檗碱。第5周麻醉处死,取右侧颈动脉组织行HE染色观察颈动脉病理改变,行免疫组织化学染色检测核因子кB的活性,逆转录聚合酶链反应检测核因子кBp65、血管细胞粘附分子1和单核细胞趋化蛋白1mRNA表达水平。结果模型组颈动脉血管内膜明显增生,内膜下和中膜可见大量泡沫细胞堆积,有明显的动脉粥样硬化斑块形成;而小檗碱组的内膜轻度增厚,内膜下有少量泡沫细胞形成。小檗碱组核因子кBp65阳性细胞数高于正常对照组(19.58±2.60比2.00±0.93,P<0.01),但明显低于模型组(37.50±2.45,P<0.01)。小檗碱组核因子кBp65mRNA(0.42±0.05)、血管细胞粘附分子1mRNA(0.61±0.11)和单核细胞趋化蛋白1mRNA(0.57±0.18)的表达高于正常对照组(分别为0.18±0.04、0.20±0.04和0.33±0.05,P<0.01),但明显低于模型组(分别为0.66±0.16、0.81±0.11和0.76±0.03,P<0.01)。核因子кB的活性与血管细胞粘附分子1和单核细胞趋化蛋白1的mRNA表达量明显相关(r=0.926,P<0.01;r=0.958,P<0.01)。结论小檗碱可能通过抑制核因子кB活性以及降低血管细胞粘附分子1和单核细胞趋化蛋白1的表达而预防家兔颈动脉粥样硬化。     

小檗碱辅助治疗糖尿病临床疗效分析

目的观察小檗碱辅助治疗糖尿病临床疗效。方法将80例糖尿病患者随机分为对照组和小檗碱组各40例，对照组给予常规控稍血糖的治疗，小檗碱组在对照组的基础上给予口服小檗碱辅助治疗：治疗前和治疗后3个月比较两组患者体重、腰围、臀围、BMI、糖化血红蛋白，空腹血糖、餐后2h血搪和血脂四项。结果与对照组比较，小檗碱组可以显著改善患者各项指标，并且差别具有统计学意义。结论小檗碱辅助治疗糖尿病疗效显著，并且安全性好，值得推广。