维胃方对胃溃疡大鼠胃黏膜MPO、H+-K+-ATP酶活性的影响

[目的]观察维胃方对胃溃疡大鼠胃黏膜髓过氧化物酶(MPO)和H⁺-K⁺-ATP酶的影响,探讨维胃方治疗胃黏膜损伤的可能机制。[方法]采用乙酸烧灼法,建立胃溃疡模型,用比色法测定胃黏膜MPO和H⁺-K⁺-ATP酶活性,并观察胃黏膜组织病理学变化。[结果]从胃黏膜大体标本、切片观察,维胃方中剂量组疗效最佳。与自愈组和模型组比较,维胃方各组胃黏膜MPO活性显著降低(P<0.01或P<0.05),其中以维胃方中剂量组值最小。维胃方各剂量组的H⁺-K⁺-ATP酶活性均高于自愈组(P<0.01或P<0.05),接近正常组(P>0.05),表明维胃方能恢复其活性。[结论]维胃方对大鼠实验性胃溃疡具有明显的保护作用,其机制可能是通过降低大鼠胃黏膜MPO活性,进而减轻炎症介质对胃黏膜的损伤。同时其能修复已损伤的胃黏膜,故能恢复H⁺-K⁺-ATP酶活性。     

合成冰片对大鼠肝CYP450酶含量及CYP3A1 mRNA表达的影响

[目的]研究冰片对大鼠肝脏细胞色素氧化酶(cytochromeP450,CYP450)含量及其亚型CYP3A1m RNA表达的影响。[方法]istar大鼠合成冰片(设0.3gk/g和0.03gk/g剂量组,1次d/,连续7d)灌胃,以溶媒羧甲基纤维素纳(CM C-Na)和苯巴比妥钠为对照组,钙沉积法提取肝微粒体,紫外分光光度法测定CYP450含量,实时定量RT-PCR法检测肝脏CYP3A1m RNA的表达。[结果]0.3gk/g合成冰片口服可诱导大鼠肝脏CYP450酶含量增高(P<0.05),CYP3A1m RNA表达上调(P<0.05)。[结论]高剂量合成冰片口服可能影响肝脏药物代谢。     

扶正排毒汤对腺嘌呤所致大鼠慢性肾功能衰竭模型的影响

[目的]观察扶正排毒汤对慢性肾功能衰竭(CRF)大鼠血浆肌酐(Scr)及尿素氮(BUN)及大鼠体质量的影响。[方法]将75只CRF大鼠,按照随机方法设立空白组、模型组、尿毒清对照组、扶正排毒汤组、西药包醛氧化淀粉组,分别用相应的药物灌胃治疗30 d,检测各组大鼠血浆Scr、BUN的含量。[结果]与包醛氧化淀粉组比较,扶正排毒汤可显著降低模型大鼠血浆中Scr、BUN含量,差异有统计学意义(P<0.01),可以提高CRF大鼠体质量(P<0.01)。与尿毒清组比较,扶正排毒汤降低模型大鼠血浆中Scr、BUN含量的作用与尿毒清组比较差异无统计学意义(P>0.05),但可以增加CRF大鼠体质量(P<0.05)。[结论]扶正排毒汤可延缓大鼠慢性肾衰竭的进程,改善大鼠预后。     

针刺对局灶性脑缺血大鼠缺血脑组织及血清白介素-8的影响

[目的]观察针刺对局灶性脑缺血大鼠脑组织及血清白介素8(IL-8)含量的影响。[方法]以热凝法阻断一侧大脑中动脉造成大鼠局灶性脑缺血模型,采用放免法测定大鼠脑组织及血清IL-8含量。[结果]脑缺血后各时段模型组与同时段假手术组及正常组比较脑组织及血清IL-8显著升高(P<0.05,P<0.01);治疗后6、12、24、48h各时段针刺组与同时段模型组比较脑组织IL-8含量明显降低(P<0.01),6、12及48h针刺组血清IL-8含量显著低于同时段模型组(P<0.05,P<0.01)。[结论]针刺可能通过抑制缺血区脑组织IL-8的合成和分泌,调节血清IL-8的含量,抑制炎性细胞的黏附及浸润,从发挥脑保护作用。     

四君子汤对脾虚大鼠不同脑区单胺类神经递质含量的影响

[目的]研究脾虚大鼠不同脑区单胺类神经递质含量的变化和四君子汤干预的途径。[方法]将60只大鼠分为空白对照组、脾虚组和四君子汤组,使用高效液相色谱法检测大鼠海马、下丘脑和纹状体中5-羟色胺(5-HT)和多巴胺(DA)的含量。[结果]与对照组比较,脾虚组大鼠各脑区内5-HT水平显著升高,DA水平显著下降(P<0.05);使用四君子汤干预后,5-HT和DA水平基本恢复正常,与空白对照组比较,无显著性差别,而与脾虚组大鼠比较,差异有显著性(P<0.05)。[结论]四君子汤可通过改善中枢单胺类神经递质含量的途径达到健脾治疗的目的。     

旋覆代赭汤及其拆方对RE大鼠血浆Na+-K+-ATP酶及Ca2+-Mg2+-ATP酶活性的影响

[目的] 探讨反流性食管炎(RE)食管黏膜血浆细胞能量代谢与黏膜损伤的关系以及旋覆代赭汤治疗RE的作用机制。[方法] 将120只Wistar大鼠按照随机数字法随机分为10组,每组12只,即正常组、模型组、旋覆代赭汤全方组(全方组)、苦降组、甘升组、升降相因组、去苦降组、去甘升组、去升降相因组和西药组;除正常组外,其余9组行"4.2 mm幽门夹+胃底2/3结扎术"造模。治疗14 d后,即造模后第22天处死,检测各组大鼠血浆Na⁺-K⁺-ATP酶及Ca²⁺-Mg²⁺-ATP酶的活性。[结果] 实验后各模型组大鼠ATP酶活性低于正常组;全方组、西药组酶活性较好,与正常组差异无统计学意义(P>0.05),与模型组相比有统计学差异(P<0.05);苦降组及去甘升组与模型组相比,差异无统计学意义(P>0.05),与全方组及西药组比较差异有统计学意义(P<0.05);正常组与其他各组比较,均有统计学差异(P<0.05);西药组与全方组比较,差异无统计学意义。[结论] 旋覆代赭汤全方组能提高模型大鼠血浆Na⁺-K⁺-ATP酶及Ca²⁺-Mg²⁺-ATP酶的活性,改善模型大鼠食管黏膜组织形态学病变,且作用优于各拆方组。     

夏枯草水提液对自身免疫性甲状腺炎大鼠5-HT和Th17的影响

[目的] 夏枯草(Prunella vulgaris L.)在临床中已经应用于治疗自身免疫性甲状腺炎(AIT), 但是机制尚不明确。本研究通过建立实验性自身免疫性甲状腺炎(EAT)大鼠模型, 研究夏枯草水提液对EAT大鼠5-羟色胺(5-HT)、5-羟色胺转运体(SERT)和Th17的作用。[方法] 水提法提取夏枯草的有效成分并采用高效液相色谱法(HPLC)对其主要活性成分进行分析; 采用皮下注射甲状腺球蛋白(Tg)联合高碘水喂养的方式建立EAT大鼠模型, 随后将EAT大鼠分为模型对照组(EAT), 夏枯草低剂量组(E-LOW), 夏枯草中剂量组(E-MID), 夏枯草高剂量组(E-HIG), 连续灌胃12周。采用酶联免疫吸附检测法(ELISA)检测大鼠血清中辅助性T细胞17(Th17)和细胞因子水平; HE染色观察大鼠甲状腺形态; 流式细胞术检测大鼠外周血单个核细胞(PBMCs)中CD4⁺IL17A⁺(Th17)淋巴细胞的水平; qRT-PCR检测脾脏中SERT水平; ELISA法检测大鼠脾脏和血清中5-HT以及血清中IL-17A, IL-6含量。[结果] 迷迭香酸(Rosmarinic Acid)是夏枯草提取物的主要成分, 夏枯草水提液治疗12周可显著降低大鼠血清TgAb(P<0.05或P<0.01), 减小甲状腺体积(P<0.01), 减轻甲状腺内炎性浸润, 降低外周血Th17比例(P<0.01)和血清IL-17A, 抑制大鼠脾脏中SERT水平(P<0.01), 提高脾脏和血清5-HT水平(P<0.01)。[结论] 夏枯草可通过提高EAT大鼠中5-HT含量, 抑制Th17细胞分化, 发挥调节免疫作用, 该研究为夏枯草治疗EAT提供新的思路。     

针刺对局灶性脑缺血大鼠缺血脑组织及血清IL-6的影响

[目的]观察针刺对局灶性脑缺血大鼠脑组织及血清白介素-6(IL-6)含量的影响。[方法]以热凝法阻断一侧大脑中动脉造成大鼠局灶性脑缺血模型,采用放免法测定大鼠脑组织及血清IL-6含量。[结果]脑缺血后3、6、12、24 h缺血组脑组织IL-6含量与正常组比较均显著增高(P<0.01),针刺后3、6、12 h脑组织中IL-6含量较同时段缺血组显著降低(P<0.01),并明显低于正常对照组(P<0.01)。脑缺血后血清中IL-6含量3 h急剧升高,3、6、12 h段缺血组血清IL-6含量与同时段假手术及正常组比较显著升高(P<0.01),治疗后3、6、12 h针刺组血清IL-6含量较同时段缺血组显著降低(P<0.01),24及48 h针刺组血清IL-6含量明显升高,与正常组及假手术组比较均有显著差异(P<0.01)。[结论]通过对IL-6的调节,发挥其抗炎、神经保护作用,促进受损神经元修复,可能针刺治疗缺血性脑卒中的作用机制之一。     

针刺对心肺复苏后家兔心肌ATP酶活性及SOD、MDA的影响

[目的]探讨针刺对心肺复苏后家兔心肌细胞三磷酸腺苷(ATP)酶活性、超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量的影响。[方法]30只家兔随机分3组,假手术(Sham)组不进行窒息和复苏;常规复苏组心搏骤停后予常规心肺复苏术;针刺复苏组心搏骤停后予常规心肺复苏术并针刺人中、内关穴。所有动物于自主循环恢复后2h取心肌组织,测定ATP酶活性、SOD活性及MDA含量。[结论]与Sham组相比,针刺复苏组、常规复苏组心肌ATP酶活性降低(P<0.01);与常规复苏组相比,针刺复苏组ATP酶活性升高(P<0.05)。复苏后两组SOD活性均低于Sham组(P<0.01),MDA含量均高于Sham组(P<0.01);针刺复苏组SOD活性高于常规复苏组(P<0.05),而MDA含量低于常规复苏组(P<0.05)。[结论]针刺人中、内关穴可增加心肺复苏后心肌组织ATP酶活性,增加SOD活力,减少MDA生成。     

双(α-呋喃甲酸)氧钒与六味地黄丸联合应用对糖尿病大鼠血糖血脂影响的实验研究

[目的]观察双(α-呋喃甲酸)氧钒(VO-FA)与六味地黄丸联合应用对糖尿病大鼠血糖血脂影响。[方法]用四氧嘧啶诱发糖尿病大鼠模型,分别以高、低剂量VO-FA联合六味地黄丸治疗,并设立正常组和模型组作对照,检测血糖、血脂变化。[结果]VO-FA联合六味地黄丸组在给药后与模型组相比表现出降糖效果(P<0.05),尤以VO-FA高剂量联合六味地黄丸组为著(P<0.01);糖尿病大鼠伴随血脂紊乱,VO-FA联合六味地黄丸与模型组相比能明显降低其总胆固醇水平(P<0.01),对其余指标无显著差异。[结论]VO-FA联合六味地黄丸能降低糖尿病大鼠的血糖和总胆固醇水平,药理机制有待于进一步研究。     

A double-blind,double-dummy,randomized controlled,multicenter trial of 99Tc-methylene diphosphonate in patients with moderate to severe rheumatoid arthritis

Background:Clinical observational studies revealed that ⁹⁹Tc-methylene diphosphonate (⁹⁹Tc-MDP) could reduce joint pain and swollenness in rheumatoid arthritis (RA) patients. This multicenter, randomized, double-blind, double-dummy study aimed to evaluate the effects of ⁹⁹Tc-MDP plus methotrexate (MTX) vs. MTX alone or ⁹⁹Tc-MDP alone on disease activity and structural damage in MTX-naïve Chinese patients with moderate to severe RA.Methods:Eligible patients with moderate to severely active RA were randomized to receive ⁹⁹Tc-MDP plus MTX (n = 59) vs. MTX (n = 59) alone or ⁹⁹Tc-MDP (n = 59) alone for 48 weeks from six study sites across four provinces in China. The primary outcomes were the American College of Rheumatology 20% improvement (ACR20) response rates at week 24 and changes in modified total Sharp score at week 48.Results:At week 24, the proportion of participants achieving ACR20 was significantly higher in the MTX + ⁹⁹Tc-MDP combination group (69.5%) than that in the MTX group (50.8%) or ⁹⁹Tc-MDP group (47.5%) (P = 0.03 for MTX + ⁹⁹Tc-MDP vs. MTX, and MTX + ⁹⁹Tc-MDP vs.⁹⁹Tc-MDP, respectively). The participants in the MTX + ⁹⁹Tc-MDP group and the ⁹⁹Tc-MDP group had significantly less important radiographic progression than the participants in the MTX group over the 48 weeks (MTX + ⁹⁹Tc-MDP vs. MTX: P = 0.03, ⁹⁹Tc-MDP vs. MTX: P = 0.03, respectively). There was no significant difference in terms of adverse events (AEs) among the groups. No serious AEs were observed.Conclusions:This study demonstrated that the combination of ⁹⁹Tc-MDP with MTX inhibited structural damage and improved disease activity in RA patients compared with MTX and ⁹⁹Tc-MDP monotherapies, without increasing the rate of AEs. Additional clinical studies of ⁹⁹Tc-MDP therapy in patients with RA are warranted.Trial Registration:Chictr.org, ChiCTR-IPR-14005684; http://www.chictr.org.cn/showproj.aspx?proj=10088.     

Effects of Xianzhen tablet on Na+ - K+ - ATPase and Ca2+ - Mg2+ - ATPase in erythrocytic membranes and viscosity of whole blood in non-insulin-dependent diabetes patients with Qi-Yin deficiency, Kidney deficiency and blood stasis

Objective: To assess the effects of Xianzhen tablet (XZT) on Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase on erythrocytic membranes, viscosity of whole blood, plasma glucose and clinical manifestations.Methods: Seventy-two cases of non-insulin-dependent diabetes mellitus (NIDDM) patients with deficiency of both Qi and Yin, deficiency of the Kidney and blood stasis were selected, and the effects of treatment on Na⁺ K⁺ -ATPase, Ca²⁺-Mg²⁺-ATPase, whole blood viscosity, blood sugar and clinical symptoms were observed.Results: In XZT group (test group), activities of Na⁺ -K⁺ -ATPase and Ca²⁺ -Mg²⁺ -ATPase rose significantly (P < 0.01,P < 0.05) after treatment. Viscosity of whole blood and clinical manifestations also improved obviously. The total effective rate in lowering plasma glucose was 77.8% with fasting blood glucose (FBG) and 69. 4% with 2 hours postprandial plasma blood glucose (2°PBG). In the control group, viscosity of whole blood and clinical manifestations had no significant improvement. Its total effective rate in lowering plasma glucose was 41.7% with FBG and 38.9% with 2°PBG.Conclusions: XZT played a certain role in increasing activities of Na⁺ -K⁺ -ATPase and Ca²⁺ -Mg²⁺ -ATPase, decreasing viscosity of whole blood and plasma glucose and improving clinical manifestations. Therefore, XZT was experimentally manifested as an effective drug in treating NIDDM patients with Qi-Yin deficiency, renal deficiency and blood stasis.     

尿电解质肌酐比、总蛋白肌酐比在体检和高血压人群中的临床应用

目的 运用尿电解质肌酐比计算膳食盐,评价人群盐摄入量。探讨尿电解质肌酐比、尿蛋白肌酐比(urinary protein/creatinine ratio, TPCR)在体检和高血压患者中的应用价值。 方法 检测948例(其中842名>50岁)健康体检者,616例住院高血压患者的尿钠、尿钾、尿总蛋白和空腹血清脂类项目,计算出尿钠肌酐比,尿钾肌酐比、尿钠钾比(Na⁺/K⁺)、TPCR和血清载脂蛋白B/A1(apoB/apoA1)。 结果 948例体检者按年龄段分组比较中,尿TPCR在50~60岁年龄组与>70岁年龄组差异最明显(P=0.000);842例>50岁体检者不同性别间比较,尿盐、尿钾差异均有统计学意义(P=0.000);高血压组与体检组比较,尿TPCR、尿Na⁺/K⁺、尿盐差异有统计学意义(P=0.000);不同级别高血压的尿盐、Na⁺/K⁺及TPCR等指标均显著增高(P=0.000);616例高血压尿总蛋白与尿Na⁺/K⁺、尿Na⁺具有相关性;图中的尿TPCR浓度随年龄加大逐渐上升,高血压尿TPCR与尿Na⁺/K⁺均显著高于正常体检者。 结论 通过尿电解质计算膳食盐,能简便有效反映人群盐摄入量的高低。尿电解质肌酐比、尿TPCR与高血压的升级及年龄增大紧密相关。     

Expression of Survivin, CyclinD1, p21^WAF1, Caspase-3 in Cervical Cancer and Its Relation with Prognosis

Summary The implications of Survivin, CyclinD1, p21^WAF1, Caspase-3 in the development, progression and prognosis in cervical cancer were investigated. By using immunohistochemical SP method, the expression of Survivin, CyclinD1, p21^WAF1, Caspase-3 was detected in 41 cases of cervical cancer, 17 cases of cervical intraepithelial neoplasia (CIN) and 10 cases of normal tissues, and their relation with pathological grade, clinical stage, metastasis and survival time was analyzed. The results showed that the positive expression rate of Survivin, CyclinD1 in cervical cancer was significantly higher than in CIN group and normal control group (P<0.05). The median survival time in the patients with cervical cancer positive for Survivin and CyclinD1 was significantly shorter than in those with negative expresion (P<0.05). The expression of both Survivin and CyclinD1 was not related with tumor grade, clinical stage and metastasis (P>0.05). The positive expression rate of p21^WAF1, Caspace-3 in cervical cancer was significantly lower than in CIN group and normal control group (P<0.05), and had a close relation with tumor grade (P<0.05). The expression of Survivin in cervical cancer in cervical cancer was negatively associated with that of Caspase-3 (P<0.01), but positively with that of CyclinD1 (P<0.01). Cox Multivariate analysis revealed that Survivin was the independent prognostic indicator influencing the survival time of the patients with cervical cancer (P<0.05). It was suggested that the high expression of Survivin or CyclinD1, and low expression of p21^WAF1 or Caspace-3 was closely correlated with the development of cervical cancer. Survivin and CyclinD1 could be used as a useful indicator to predict the prognosis of cervical cancer. LU Shi, female, born in 1967, Doctorial Candidate     

加味二陈汤对ApoE-/-小鼠脂质代谢及肝细胞形态的影响

目的观察加味二陈汤对Apo E-/-小鼠血脂的影响。方法 44只Apo E-/-小鼠以高脂饲喂养4周构建AS小鼠模型,分别用辛伐他汀、加味二陈汤对小鼠灌胃给药,8周后处死小鼠,酶法检测血清血脂;每周称取并记录小鼠体重;油红O染色观察小鼠主动脉管腔内粥样斑块;HE染色观察小鼠主动脉管腔内粥样斑块沉积及肝细胞形态。结果加味二陈汤可显著降低小鼠血清中TCHOL、LDL-C水平(P<0.01);各组小鼠体重均有所增加,但模型组小鼠体重略高于空白对照组和加味二陈汤组;油红O染色结果显示加味二陈汤可显著减少Apo E-/-小鼠主动脉管腔内粥样斑块的面积;小鼠主动脉HE染色示加味二陈汤组小鼠主动脉内有脂质沉积斑块较模型组明显减少;肝细胞切片HE染色发现加味二陈汤组小鼠肝细胞的病变程度较轻,肝小叶结构较清晰。结论加味二陈汤能有效降低Apo E-/-小鼠血清中有关脂质的含量,调节小鼠脂质代谢,缓解动脉粥样硬化进程。     

Studies on the calcium antagonistic action of tetrandrine: VI. Comparison of effects of tetrandrine,verapamil and propranolol on myocardial blood flow

Summary By⁸⁶RbCl-extraction method, the effects of tetrandrine (Tet), verapamil (Ver) and propranolol (Pro) on myocardial blood flow of mice were studied. Both I.P. Tet 100 mg/kg and Ver 5 mg/kg increased the blood flow, whereas I.P. Pro 30 mg/kg did not. Pro counteracted significantly the increase of myocardial blood flow by isoproterenol, while Tet and Ver failed. On the other hand, Tet and Ver markedly antagonized the increase of myocardial blood flow by CaCl₂, but Pro did not. The results indicate that unlike the β-receptor blocking agent Pro, Tet may be a calcium antagonist similar to Ver.     

The effect of magnesium on erythrocytic electrolytes in digitalis toxicity

Summary Concentrations of K⁺, Na⁺ and Mg⁺⁺ were measured in plasma (K⁺ _e, Na⁺ _e, Mg⁺⁺ _e) and in erythrocytes (K⁺ _i, Na⁺ _i, Mg⁺⁺ _i) in patients with digitalis toxicity before and after administration of Mg. K⁺ concentration in 24-hour urine was also measured. 70 persons were divided into 5 groups: (1) 11 normal persons as controls; (2) 19 patients with congestive heart failure, in whom Mg⁺⁺ _i and Mg⁺⁺ _e concentrations were found to be lower than that of the control group; (3) 16 patients with digitalis toxicity treated by Mg⁺⁺, whose K⁺ _i concentration increased much quicker, and Na⁺ _i and Na⁺ _i/K⁺ _i decreased remarkably in comparison to non-Mg treatment group; (4) 12 patients with digitalis toxicity not treated by Mg⁺⁺: in these the above-mentioned changes were not significant; (5) 12 patients with arrhythmia of other causes treated by Mg⁺⁺: whose K⁺ _i also increased significantly on the 3rd day after treatment. K⁺ concentration in 24-hour urine was much lower in Mg treatment group than in non-Mg treatment group. Besides, acute digitalis toxicity was observed in experimental dogs. The concentration of K⁺ _i recovered much quicker in Mg treatment group than in control group. These findings indicate that hypomagnesemia may induce digitalis toxicity. In this paper the possible mechanism of the therapeutic effect of Mg in the treatment of digitalis toxicity is discussed.     

Shkbp1缺失对小鼠T淋巴细胞系亚群的影响

目的探讨Shkbp1缺失小鼠(Shkbp-1~(-/-))的血液、骨髓、脾脏中血液细胞分类和T细胞亚群的变化。方法采用Shkbp-1~(-/-)转基因小鼠,经PCR鉴定基因型;利用全自动血液检测仪测定血液细胞分类;采用流式细胞仪检测Shkbp-1~(-/-)和对照组小鼠血液、骨髓、和脾脏中T淋巴细胞亚群。结果血常规结果:中性粒细胞和嗜酸性粒细胞有增高趋势,且有显著差异。淋巴细胞未见显著差异。流式结果显示:对照组血液中CD4~+CD8~+双阳性细胞降低,骨髓中CD3~+、CD4~+升高。但脾脏组织中,其CD3~+、CD4~+、CD8~+、CD4~+CD8~+双阳性细胞均呈下降趋势。结论 Shkbp1参与血液细胞的成熟分化,影响了免疫细胞数量,本研究为探索Shkbp1如何参与血液细胞的分化奠定了研究基础。     

双哌嗪类化合物的合成及钙通道阻滞活性

为寻求活性更好、毒性更低的新结构类型钙通道阻滞剂,以氟桂利嗪为先导化合物,设计合成了一系列双哌嗪类新化合物,并经光谱证明其结构。初步药理实验结果表明,9个新化合物在⁴⁵Ca²⁺跨膜内流动药理实验中,对大鼠主动脉电压依赖型钙离子通道（PDC）均有钙阻滞活性,且部分化合物的活性强于阳性对照药硝苯吡啶。