还原型谷胱甘肽联合甘草酸二铵对腹部开放伤后海水浸泡犬肝功能损伤的治疗作用

Objective To investigate effect of reduced glutathione and diammonium glycyrrhizinate on the treatment of hepatic damage in experimental dogs following open abdominal injuries coupled with seawater immersion. Methods Twenty-four dogs with open abdominal injuries were randomly divided into 3 groups: the control group (given with simple observation after 1.5 h seawater immersion); the routine treatment group (given routine care and fluid transfusion after 1.5 h seawater immersion) ; the hepatic treatment group (given routine are, fluid transfusion and hepatic treatment as well, after 1.5 h seawater immersion). Each group consisted of 8 dogs. Blood samples were taken at different time points to measure total bilirubin (TB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), prothromin time (PT), endotoxin, tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), and pathological examination was also made at the same time. Results For the control group, contents of TB, ALT, AST and LDH increased significantly and survival time was less than 24 hours. Contents of TB, ALT, AST and LDH of the routine treatment group also increased significantly, but survival time of all the experimental animals was mere than 24 hours. Reduced glutathione and diammonium glycyrrhizinate could reduce the extent of lesion quite significantly 12～24 hours following open abdominal injuries. Conclusions Reduced glutathione and diammonium glycyrrhizinate seemed to have good effects on the treatment and prevention against hepatic damage induced by trauma coupled with seawater immersion. It could be used as a primary means for the treatment of such kind of hepatic damage.     

各种肝病的肝纤维化标志改变的探讨

目的 :探讨各种肝病患者血清肝纤维化标志的改变 ,甘草酸二胺注射液对肝脏炎症、纤维化指标的作用。方法 :用放免法检测透明质酸 (HA)、层粘蛋白 (LN)、Ⅲ型前胶原多肽 (PCⅢ )。结果 :急性肝炎的三种肝纤指标均升高 (P <0 0 5 )。急黄肝高于急无黄肝 (P <0 0 5 )。慢性肝炎 1 1 2例 ,三项肝纤指标显著高于正常对照 (P <0 0 5 )。慢肝重度显著高于慢肝轻度 (P<0 0 0 1 )。肝硬化的三项肝纤指标又显著高于慢肝 (P <0 0 0 1 ) ,其它肝病的肝纤指标也升高。 2 5例慢肝用甘草酸二胺注射液治疗 2月 ,ALT、AST、GGT显著降低 (P <0 0 1 )。三项肝纤指标中HA降低较显著 (P =0 0 5 ) ,LN和PCⅢ虽有降低 ,但差异不明显 (P =0 4 5 9,P =0 1 92 )。结论 :各种肝病的三项肝纤维化指标均升高 ,以慢肝重度 ,肝硬化升高明显。甘草酸二胺注射液治疗有抗炎及改善肝纤维化的作用     

W／O／W型甘草酸单铵盐口服复乳的处方设计及其理化特性研究

采用均匀设计，以乳剂的稳定性参数为考察指标，考察了初乳乳化剂、复乳乳化剂、乳化时间等因素对复乳稳定性的影响；筛选出Ｗ／Ｏ／Ｗ型甘草酸单铵盐口服复乳的优化处方和工艺，并对复乳的主要理化特性和物理稳定性进行了考察。     

Chemotherapie mit Cisplatin-Bleomycin und nachfolgende Strahlentherapie bei fortgeschrittenen Kopf-Hals-Tumoren

Summary 42 patients with advanced stage III and IV squamous cell carcinoma of the head and neck were treated with initial cisplatin and bleomycin chemotherapy and subsequent radiotherapy. 39 were evaluable for results, and 3 for toxicity only. 8 patients suffered from stage III and 31 from stage IV tumors, of these 10 with distant metastases. 5 patients underwent later a rescue operation. 27 were previously untreated (= group A) including 2 cases with localized relapses beyond the margins of surgical and/or radiotherapeutic treatment fields. 12 patients had a recurrence within pretreated areas (= group B). The induction chemotherapy alone showed the following results: In group A 4 (15%) CR, 10 (37%) PR, 7 (26%) MR; in group B 3 (25%) PR, 2 (17%) MR. The subsequent radiotherapy mostly consisted of a 65 Gy tumor dose given in 61/2 weeks. The results after completion of the combined modality therapy were: In group A 44% CR, 28% PR; in group B 10% CR and 30% PR. No patient resistant to the initial chemotherapy responded to the radiotherapy. The median survival time of stage III patients was 20 months but only 7 months in stage IV patients. 4 of all live with NED now between 30+ and 41+ months; 1 patient is alive with relapse. All the others are dead after a survival time of max. 32 months, included the 5 with rescue operation. In general, hematologic and renal toxicities were not severe, but nausea and vomiting were the worst tolerated side effects. 1 patient died from septic myocarditis having a WBC nadir of 2000/µl, probably due to additional immunologic deficiency because of inactive liver cirrhosis. The poor results concerning NED survival are discussed. We conclude, that an initial chemotherapy with CDDP and BLM gives good remission effects but its combination with radiotherapy at present fails to produce a NED survival benefit. Further efforts are necessary to improve the CR and the long time survivor rates.

Die Autoren danken folgenden Kollegen für ihre Mitarbeit: Drs. Garbea (HNO), B. Bienko, M. Danker, N. Birke, M. Klessing, K. Lottner, W. Palm     

甘草酸二铵对马兜铃酸致肾小管上皮细胞损害保护作用的实验研究

目的　探讨甘草酸对马兜铃酸 (aristolochic acid,AA)肾损害的保护作用 ,观察甘草酸是否可以减轻 AA对培养的肾小管上皮细胞的损害 ,并初步探讨其可能机制。方法　 5 % FCS RPMI- 16 4 0培养肾小管上皮细胞株 (L L C- PK1) ,采用结晶紫染色法观察细胞增殖 ;荧光染色观察活细胞数目 ;酶动力学检查 L DH活性 ,比色法检测 NAG水平 ;透射电镜观察细胞超微细胞结构。结果　1AA4 0、80、16 0μg/ ml可明显抑制细胞增殖 ,结晶紫 OD值显著减少 ,与无 AA对照组比较 P<0 .0 1。 2甘草酸二铵 (diammoniumglycyrrhizinate,DG)在 5、10、2 5 μg/ ml时结晶紫 OD值与无甘草酸对照组比较 P>0 .0 5 ,甘草酸在 5 0 μg/ ml时 P<0 .0 5 ,10 0 μg/ ml、2 0 0μg/ ml时 P<0 .0 1,提示大剂量甘草酸可改善 AA抑制细胞增殖的作用。 3在 AA4 0μg/ ml作用下随着时间延长 ,无甘草酸组的细胞存活数目逐渐减少 ,而甘草酸 (10 0μg/ ml、2 0 0μg/ ml)作用组 ,活细胞数目明显增多 ,提示高浓度甘草酸对细胞损伤有一定的保护作用。4甘草酸在 5、10、2 5 μg/ ml时 ,L DH释放率、NAG酶水平与无甘草酸对照组比较 P>0 .0 5 ,甘草酸在 5 0 μg/ ml时 P<0 .0 5 ,甘草酸在 10 0μg/ ml、2 0 0μg/ ml时 L DH释放率、NAG酶明显减少 ,与无甘草     

甘草酸二铵对关木通所致大鼠肾脏纤维化的影响

目的探讨甘草酸二铵对关木通所致大鼠肾脏纤维化的影响，为临床防治肾脏纤维化提供理论依据。方法将18只大白鼠随机分成3组，正常对照组、关木通组、甘草酸二铵与关木通联合组各6只。在实验前及实验第2，3，4，5，6周分别采血，测定血肌酐(SCr)、血尿素氮(BUN)、血钾、血钠、血钙等生化指标以及Ⅲ型前胶原(PCⅢ)、血清透明质酸(HA)、层粘蛋白(LN)等放射免疫指标。第6周时处死动物取肾脏作组织形态学特殊染色检查。结果关木通组与联合组用药后血生化、放免指标均明显上升(P＜0.05或P＜0.01)。联合组与关木通组肾脏纤维化程度差异无显著性(P＞0.05)。结论甘草酸二铵对关木通所致的急、慢性肾损伤无明确的防治作用；血放射免疫指标(PCⅢ、HA、LN)可作为早期慢性肾间质纤维化的重要临床观察指标。     

甘草酸二铵对大鼠心肌缺血再灌注心律失常的影响

目的观察甘草酸二铵(DG)对大鼠心肌缺血再灌注心律失常的影响.方法在大鼠心肌缺血10min再灌注30min损伤模型上,监测肢体II导联ECG.术后用分光光度法分别测定心肌组织中丙二醛(MDA)、Na -K -ATP酶、超氧化物歧化酶(SOD)及血清乳酸脱氢酶(LDH),肌酸激酶(CK)含量.结果DG能显著降低再灌注心律失常发生率及评分(P<0.01),也能明显减少心肌组织MDA含量(P<0.01),增加SOD和Na -K -ATP酶活性,还能减少心肌CK、LDH的释放(P<0.01).结论DG具有抗心肌缺血再灌注心律失常的作用,可能与降低心肌脂质过氧化和增强氧自由基清除酶的活性有关.     

抗甘草酸二铵抗血清的制备

目的通过人工抗原的构建,制备抗甘草酸二铵（DG）的特异性抗血清。方法采用碳二亚胺法将DG与牛血清蛋白（BSA）和鸡卵清蛋白（OVA）共价偶联,分别合成免疫抗原DG-BSA和包被抗原DG-OVA。用合成的人工抗原免疫家兔,制得抗甘草酸二铵的特异性抗血清,并通过酶联免疫方法（ELISA）对抗血清进行鉴定。结果制备了抗甘草酸二铵的多克隆抗体,获知理想的包被抗原的浓度为200ng／mL,抗血清的工作浓度为1：10000,雌、雄家兔抗血清的效价分别为1：51200和1：25600。结论采用化学反应构建人工抗原的方法,可以制备出针对甘草酸二铵的特异性抗血清,从而为甘草酸二铵的鉴定及体内代谢的免疫学分析研究奠定了基础。     

HPLC测定复方硫酸沙丁胺醇双层片含量的研究

目的建立复方硫酸沙丁胺醇双层片中硫酸沙丁胺醇、富马酸酮替芬及甘草酸单铵盐的HPLC测定方法。方法采用高效液相色谱法,外标法。色谱条件:采用Luna 5u C18(250×4.6 mm)色谱柱。检测波长为276 nm,考察了方法的线性范围、回收率、精密度、重复性等指标。结果所考察的浓度范围内具有良好线性,硫酸沙丁胺醇、富马酸酮替芬及甘草酸单铵盐的线性范围分别是30~150μg/m l(r=0.9998)、9.15~45.76μg/m l(r=0.9990)、及0.66~3.3 mg/m l(r=0.9999),平均回收率分别为100.1%(RSD为0.12%)、99.98%(RSD为0.46%)、99.59%(RSD为1.01%)(n=9)。结论方法准确简便,重复性好,适用于该制剂的含量测定。     

基于白细胞介素 13/信号传导和转录激活因子 6信号通路研究甘草酸二铵对慢性阻塞性肺疾病大鼠气管黏液高分泌的影响

目的基于白细胞介素 13(IL-13)/信号传导和转录激活因子 6(STAT6)信号通路观察甘草酸二铵盐对慢性阻塞性肺疾病( COPD)大鼠气管黏液高分泌的影响。方法 2019年 6月至 2020年 2月,从珠海百试通生物科技有限公司购买健康雄性 SD大鼠。将 SD雄性大鼠按随机数字表法分为正常组、模型组、盐酸氨溴索组和甘草酸二铵低、中、高剂量组,每组 15只。采用香烟烟熏联合脂多糖( LPS)建立 COPD大鼠模型,除正常组和模型组注射生理盐水外,其余各组均于尾部静脉注射相应剂量的药物,每天 1次,持续 14 d。通过检测各组大鼠的肺阻力(RI)、肺顺应性( Cdyn)以及酚红排痰实验反映大鼠肺功能变化情况; ELI-SA检测肺泡灌洗液中 IL-13的水平变化; HE染色反映肺组织的病理学变化;实时定量荧光 PCR(qRT-PCR)和 Western blotting检测各组肺组织中 IL-13、STAT6和黏蛋白 5AC(MUC5AC)mRNA及蛋白表达水平。结果与正常组相比,模型组大鼠 Cdyn降低, RI［( 2.39±0.30)cmH2O·mL-1·s-1比( 0.85±0.11)cmH2O·mL-1·s-1］、排痰量［( 1.09±0.14)mg/L比( 0.55±0.07)mg/L］、肺泡灌洗液中 IL-13［(34.28±5.88)ng/L比( 10.36±1.67)ng/L］水平显著升高( P<0.05),肺组织出现病理学损伤, p-STAT6/STAT6［(1.33±0.23)比( 0.72±0.14)］水平以及 IL-13蛋白［(0.47±0.07)比( 0.17±0.03)］和 MUC5AC mRNA及蛋白［(0.78±0.15)比( 0.15±0.04)］水平均有升高( P<0.05);与模型组相比,甘草酸二铵低、中、高剂量组和盐酸氨溴索组 Cdyn增加, RI、排痰量、肺泡灌洗液中 IL-13水平显著下降( P<0.05),肺组织损伤程度降低, p-STAT6/STAT6以及 IL-13蛋白和 MUC5AC mRNA及蛋白水平均有降低( P<0.05);其中甘草酸二铵组作用效果最为明显。结论甘草酸二铵能抑制 COPD模型大鼠 IL-13/STAT6信号通路,并可能藉此减轻气管黏液高分泌,改善气管阻塞。