汉防己甲素联合GP方案治疗晚期非小细胞肺癌的随机对照临床研究

目的：评价汉防己甲素注射液联合吉西他滨（gemcitabine，G）、顺铂（cisplatin，P）方案治疗晚期非小细胞肺癌（a—NSCLC）的临床疗效、不良作用。方法：240例a—NSCLC患者随机分为汉防己甲素联合GP方案组和单纯GP方案组。吉西他滨1000mg／m。于第1、8天静滴，顺铂75mg／m2于第1天静滴，治疗组同时加用汉防己甲素注射液150mg／d静滴，第1—10天连续给药，对照组单纯化疗，每21天为1个周期。按照RE—CIST标准评价近期疗效，参照Kamofsky评分及体重变化评价生活质量，按照NCICTC3．0版标准评价毒性反应。结果：219例患者可评价疗效。治疗组近期客观有效率36．1％，对照组为24．3％，P=0．057；治疗组近期疾病控制率63．9％，对照组为52．3％，P=0．081；1年生存率两组分别为45．7％、31．3％，P=0．059；治疗后两组KPS评分提高率分别为49．1％、32．4％，P=0．012；体重增加率分别为28．7％、16．2％，P=0．027。治疗组的2—4度白细胞、血小板减少及恶心、呕吐等发生率分别为38．0％、19．4％、46．3％、16．7％，均低于对照组53．2％、34．2％、63．0％、27．9％，均P〈0．05，而局部刺激为2．8％，略高于对照组0．O％，P〉0．05；上述不良反应均可耐受及预防。结论：汉防己甲素可能具有提高a—NSCLC患者化疗的近期疗效、延长生存期的作用，无明显不良作用，同时可减轻化疗不良反应、改善患者的生活质量，在一定程度上提高机体对化疗的耐受性，是a—NSCLC综合治疗的较好选择。     

汉防己甲素滴眼液对家兔眼刺激性实验研究

目的观察不同浓度汉防己甲素滴眼液对兔眼的刺激反应。方法 20只家兔（40眼）随机分为0.1%Tet、0.2%Tet、0.5%Tet、1%Tet、赋形剂5组,每只家兔右眼分别滴上述各组滴眼液0.1 ml,左眼滴等体积的生理盐水做对照,每天4次,连续1周,停药后继续观察7d,用裂隙灯观察兔眼结膜、角膜、虹膜的刺激反应并评分。结果 1%Tet组中4只动物中的2只出现鲜红色结膜充血,角膜散在点状混浊,停药后2~3d消失,其余各组动物未见异常反应。结论汉防己甲素滴眼液对兔眼无明显刺激性。     

Tetrandrine down-regulates ERK/NF-κB signaling and inhibits activation of mesangial cells

Objectives

Tetrandrine (TET), a bisbenzylisoquinoline alkaloid isolated from Stephania tetrandra S. Moore of the Menispermaceae, possesses anti-inflammatory activity. We examined the effect of tetrandrine on interleukin-1β (IL-1β)-provoked inflammatory response in mesangial cells.

Materials and methods

Primary rat mesangial cells (PRMCs) were treated with IL-1β to induce inflammation to resemble glomerulonephritis. Cell viability, morphology and NO production were evaluated. Western blotting was applied for expression of matrix metalloproteinase-9 (MMP-9), inducible NO synthase (iNOS), extracellular signal-regulated kinase (ERK) and NF-κB-related molecules. Electrophoretic mobility shift assay was performed to examine the DNA-binding activity of NF-κB.

Results

TET, at concentrations up to 10 μg/ml, had no significant effect on viability of PRMCs. At non-toxic concentrations, TET inhibited expression of phosphorylated ERK as well as phosphorylated IKK, enhanced degradation of IκBα and reduced the DNA-binding activity of NF-κB in IL-1β-primed PRMCs, suggesting an inhibitory effect on ERK/NF-κB signaling. TET attenuated the IL-1β-provoked expression of iNOS and release of NO. Moreover, both the protein expression and gelatinase activity of MMP-9, but not MMP-2, were markedly suppressed by TET.

Significance

TET down-regulated ERK/NF-κB signaling and inhibited the expression of inflammatory mediators NO and MMP-9. Since these mediators appear to activate mesangial cells, TET may play an important role in prevention of glomerulonephritis.     

Synergistic interaction between tetrandrine and chemotherapeutic agents and influence of tetrandrine on chemotherapeutic agent-associated genes in human gastric cancer cell lines

PURPOSE: Tetrandrine (Tet), a bis-benzylisoquinoline alkaloid that was isolated from the dried root of Hang-Fang-Chi (Stephania tetrandra S. Moore), is well known as processing a marked antitumor effect in vitro and in vivo. The aim of this study was to assess the interaction between tetrandrine and chemotherapeutic agents widely used in gastric cancer treatment, and to investigate the influence of tetrandrine on chemotherapeutic agent-associated gene expression and apoptosis. METHODS: Synergistic interaction on human gastric cancer BGC-823 and MKN-28 cells was evaluated using the combination index (CI) method. The double staining with both Annexin-V-FITC and PI was employed to distinguish the apoptotic cells from living cells. Expression of chemotherapeutic agent-associated genes, i.e., excision repair cross-complementing 1 (ERCC1), thymidylate synthase (TS), class III beta-tubulin (beta-tubulin III) and tau, of BGC-823 cells with or without tetrandrine treatment were measured by real-time quantitative PCR. RESULTS: Tetrandrine had a synergistic effect on the cytotoxicity of chemotherapeutic agents in both two gastric cancer cell lines. The combination of tetrandrine and chemotherapeutic agents could also induce apoptosis in a synergistic manner. Tetrandrine could suppress the mRNA expression of ERCC1, TS, beta-tubulin III and tau. Most prominently, ERCC1, TS and beta-tubulin III mRNA levels were markedly suppressed at 0.29-, 0.12- and 0.60-fold, respectively, by the presentation of tetrandrine. CONCLUSION: Tetrandrine appears a promising candidate for combining with three chemotherapeutic agents. The possible mechanisms might be the synergistic apoptotic effect and the downregulation of chemotherapeutic agent-associated genes.     

汉防己甲素对成纤维细胞Ⅰ型胶原蛋白合成的影响

目的　探讨汉防己甲素预防和治疗增生性瘢痕的可行性。方法　对增生性瘢痕中的成纤维细胞进行培养 ,然后加入不同浓度的汉防己甲素 ,培养后继续观察成纤维细胞合成胶原蛋白的能力的变化。结果　汉防己甲素可以抑制成纤维细胞合成胶原蛋白。结论　汉防己甲素对成纤维细胞胶原蛋白的合成具有抑制作用 ,因此它可能对增生性瘢痕具有预防和治疗作用     

Effects of funnel web spider toxin on Ca currents in neurohypophysial terminals

Funnel web spider toxin (FTX) is reportedly a specific blocker of P-type Ca²⁺ channels. The effects of FTX on the Ca²⁺ currents of isolated neurohypophysial nerve terminals of the rat were investigated using the ‘whole-cell’ patch-clamp technique. Both the transient and long-lasting Ca²⁺ current components were maximally elicited by depolarization from a holding potential equal to the normal terminal resting potential (−90 mV). Externally applied FTX inhibited the high-voltage-threshold, transient component of the Ca²⁺ current in a concentration-dependent manner, with a half-maximal inhibition at a dilution of approximately 1: 10000. FTX also shifted the peak current of the I–V relationship by + 10 mV. The long-lasting Ca²⁺ current component, which is sensitive to L-type Ca²⁺ channel blockers, was insensitive to FTX. The transient current, which is sensitive to ω-conotoxin GVIA, was completely blocked by FTX. These results suggest that there could be a novel, inactivating Ca²⁺ channel in the rat neurohypophysial terminals which is affected by both N-type and P-type Ca²⁺ channel blockers.     

粉防己碱对瘢痕成纤维细胞活性功能的影响

目的　观察粉防己碱对体外培养的巨噬细胞介质介导瘢痕成纤维细胞活性功能的调控作用 ,并探讨其在瘢痕防治中的意义。方法　取 5例手术切除的人增生性瘢痕组织标本行瘢痕成纤维细胞体外培养 ,于传代培养至第 4代的成纤维细胞 (5× 10 4)中分组加入巨噬细胞介质、粉防己碱继续培养 ,然后分别用3 H TdR和3 H 脯氨酸脉冲标记 ,放射性核素液闪烁仪定量检测各组3 H TdR和3 H 脯氨酸掺入值。并采用三维培养方法测定体外模拟瘢痕样组织的收缩指数变化。结果　粉防己碱 3mg/L不抑制细胞DNA合成时 ,即可明显减少瘢痕成纤维细胞 3 H 脯氨酸掺入值 ,由对照组的 94 5± 191减少至6 82± 2 0 5 (P <0 .0 5 ) ;并能显著降低巨噬细胞介质介导的瘢痕成纤维细胞3 H TdR掺入值和3 H 脯氨酸掺入值 ,由单纯介质组的 2 75 6± 2 4 4、1384± 2 93分别降低至 194 8± 2 82、10 34± 14 2 (均P <0 .0 1)。粉防己碱 1mg/L即可降低体外瘢痕样组织的收缩指数 (P <0 .0 1)。结论　粉防己碱对体外培养的巨噬细胞介质介导瘢痕成纤维细胞增殖、胶原合成以及收缩三方面具有抑制效应 ,可望在增生性瘢痕的防治中发挥重要作用。     

粉防己甲素联合氟桂利嗪胶囊治疗偏头痛的临床观察

目的观察粉防己甲素联合氟桂利嗪胶囊对偏头痛患者治疗效果及安全性。方法 70例偏头痛患者随机分为对照组36例(氟桂利嗪胶囊)和治疗组34例(粉防己甲素片联合氟桂利嗪胶囊)。观察两组患者视觉模拟量表(VAS)评分、口述疼痛分级法(VRS)评分与生存质量评分(SF-36)变化。结果两组患者年龄、病程、治疗前VAS、VRS积分及SF-36评分差异无统计学意义(P0.05)。两组治疗后VAS、VRS积分均显著降低,治疗组优于对照组(P0.05)。治疗组患者生活质量各维度评分较治疗前均有显著提高,差异有统计学意义(P0.05)。对照组患者生理功能、生理职能、躯体疼痛、总体健康、精力及社会功能较治疗前比较有明显提高(P0.05)。治疗后两组比较,治疗组各维度评分均高于对照组,其中生理职能、躯体疼痛及总体健康评分差异均有统计学意义(P0.05)。结论粉防己甲素片能显著提高氟桂利嗪胶囊治疗偏头痛的临床效果,改善患者的生活质量,其作用机制有待进一步深入研究。     

粉防己碱抑制肝纤维化大鼠肝组织c-fos和c-jun mRNA表达

目的 探讨粉防己碱（tetrandrine,Tet)对肝纤维化大鼠肝组织c—fos及c-jun mRNA表达的影响。方法 皮下注射四氯化碳诱导大鼠肝纤维化模型，同时给予不同剂量(5、10、20mg/kg)Tet灌胃，采用RT—PCR法检测肝组织c—fos及c—jun mRNA的表达。结果 不同剂量Tet能不同程度地抑制肝纤维化大鼠肝组织c—fos及c-jun mRNA的表达。结论 Tet能有效地在转录及其上游水平抑制肝脏胶原合成，从而发挥抗肝纤维化作用。