粉防己碱对转化生长因子β促瘢痕胶原基质收缩效应的阻断作用

目的 :研究粉防己碱对转化生长因子 β促瘢痕胶原基质收缩效应的作用。 方法 :将瘢痕成纤维细胞、胶原基质和转化生长因子 β共同构成体外瘢痕实验模型 ,观察粉防己碱对其收缩指数的影响。结果 :粉防己碱对转化生长因子β促瘢痕胶原基质收缩具有阻断作用 ,并呈剂量依赖关系。结论 :这一效应可能是粉防己碱抗瘢痕纤维化的机制之一。     

粉防己碱抑制瘢痕成纤维细胞诱导胶原基质的收缩

采用成纤维细胞三维培养方法观察了粉防己碱对人瘢痕成纤维细胞诱导胶原基质收缩的影响，结果表明粉防己碱１μｇ／ｍｌ、４μｇ／ｍｌ能有效地抑制体外瘢痕成纤维细胞与胶原基质网的收缩，呈剂量效应关系     

粉防己碱对PDGF、TGF-β诱导瘢痕成纤维细胞增殖与胶原合成的抑制作用

目的:探讨粉防己碱对血小板衍生生长因子(PDGF-BB)、转化生长因子β(TGF-β)诱导人增生性瘢痕成纤维细胞增殖和胶原合成的干预作用.方法:体外培养的人增生性瘢痕成纤维细胞加入PDGF-BB、TGF-β、粉防己碱, 用3H-TdR掺入法和3H-脯氨酸掺入法测定粉防己碱干预下PDGF-BB、TGF-β诱导人增生性瘢痕成纤维细胞增殖和胶原合成作用的变化.结果:粉防己碱在不抑制瘢痕成纤维细胞DNA合成的药物浓度(3μg/ml)时即可显著抑制其胶原合成,并可显著抑制PDGF-BB和TGF-β诱导的实验细胞DNA及胶原合成.结论:粉防己碱可抑制PDGF-BB、TGF-β诱导的人增生性瘢痕成纤维细胞增殖和胶原合成.     

粉防己碱抑制瘢痕形成机理的研究

目的：探讨粉防己碱对瘢痕形成的抑制作用及其机理。方法：采用瘢痕成纤维细胞体外培养和兔实验性瘢痕模型,观察粉防己碱对瘢痕成纤维细胞增殖和胶原合成的作用。结果：体外实验粉防己碱组^3H－TdR掺入率和^3H－脯氨酸掺入率均较对照组明显降低,呈剂量依赖关系;动物实验粉防己碱能明显减少瘢痕组织中成纤维细胞的数量,降低胶原面密度,减轻瘢痕纤维化程度。结论：粉防己碱对瘢痕成纤维细胞过度增殖和胶原沉积具有抑制作用,可能是其抗瘢痕纤维化的主要机制之一。     

粉防己碱对人增殖性瘢痕成纤维细胞增殖的抑制作用

目的：探讨粉防己碱对人增殖性瘢痕成纤维细胞增殖的影响。方法：取手术切除的人增生性瘢痕组织标本,分离培养成纤维细胞,加入不同浓度粉防己碱进行干预,MTT比色法检测各组瘢痕成纤维细胞增殖效应。结果：粉防己碱药物浓度由5μg／ml升至80μg／ml时,瘢痕成纤维细胞增殖活性逐渐降低,呈明显剂量依赖性。结论：粉防己碱对人增殖性瘢痕成纤维细胞增殖具有明显抑制作用。     

粉防已碱和小檗胺抑制前列腺素和白三烯的生成

粉防己(Stephania tetrandra Moore)块根中的粉防已碱从中国古代起就用于风湿性疾病的治疗。有人认为它通过抑制胶原合成而具有治疗矽肺的功效。胶原合成的增加很可能是二氧化硅激活巨噬细胞后而引起的剧烈的炎性改变的结果。因此,作者推测粉防己碱可能作用于炎症发生过程的某个环节。粉防己碱能抑制中性白细胞和单核细胞的数种功能,包括粘附、迁移和超氧化物的产生,但不抑制脱颗粒作用。还能抑制抗原和有丝分裂原诱导的淋巴细胞转化,自然杀伤细胞(NK)毒性、肥大细胞组织胺释     

粉防己碱防治肝纤维化的作用机制研究

防己最早记载于《神农本草经》,并被列为下品。李时珍的《本草纲目》中记载,防己具有祛风止痛、利水消肿的作用。临床发现,中药饮片粉防己中的有效成分粉防己碱对肝纤维化的治疗有着良好的疗效,主要从抑制肝星状细胞的活性、抑制储脂细胞增殖、调节细胞周期、抑制细胞外基质的合成、抑制胶原合成及减少脂质过氧化损伤等方面达到治疗的目的。本文通过对粉防己碱及其配伍用药等治疗肝纤维化的机制进行综述,以期为进一步开发研究提供借鉴。     

粉防己与其主要组分粉防己碱效、毒作用及关系初探

目的:结合粉防己碱在生药及水提物中含量的测定,从效、毒两个维度来阐释粉防己与其主要生物碱粉防己碱的作用差异及两者之间的关系。方法:HPLC测定粉防己水提物中粉防己碱的含量的基础上,确定粉防己碱给药剂量,分别采用热板法、小鼠耳肿胀法对粉防己与粉防己碱的镇痛、抗炎作用进行比较研究;同时,选取给药12,24 d以及停药12 d 3个不同时间点实验动物总蛋白(TP),白蛋白(ALB),丙氨酸氨基转氨酶(ALT),天冬氨酸氨基转氨酶(AST),总胆红素(TBIL)作为观测指标,对粉防己与粉防己碱的肝脏毒性进行探查和比较。结果:1防己药材中粉防己碱的含量8.99 mg·g-1,粉防己水提液中粉防己碱的转移率为30.03%;2粉防己与粉防己碱均有明显的镇痛作用,但从短期镇痛效果而言,以粉防己碱为佳,从长期镇痛效果而言,以粉防己水提物为佳。粉防己碱的抗炎效果相对优于粉防己水提物的抗炎效果,但两者相比无显著性差异。3粉防己水提物和粉防己碱给药均可以造成一定程度的肝细胞受损,但两者的作用机制不同,且粉防己水提物造成的肝脏损伤停药后具有可逆性,而粉防己碱造成的肝脏损伤在停药后则继续发展。结论:粉防己碱作为粉防己的主要组分,并不能够完全表征粉防己的药效及毒性,同样的,粉防己中的其他组分也对粉防己碱的毒性作用没有明显的监制作用。粉防己碱与粉防己的效、毒作用表现及机制并不相同。     

粉防己碱对人皮肤成纤维细胞生长的抑制作用观察

观察粉防己碱对体外培养人皮肤成纤维细胞生长的影响。结果表明：粉防己碱能抑制成纤维细胞生长，抑制作用与浓度、时间呈正相关。据此结果，作者认为粉防己碱在增生性瘢痕的防治中有应用价值。     

粉防己碱对大鼠心肌缺血诱发心律失常的保护作用

粉防己碱Tet,又名汉防己甲素是中药汉防己中提取的主要生物碱。粉防己碱作为中药来源的钙拮抗剂之一,其降压,舒血管,降低心肌收缩力等心血管作用已被广泛研究,但对心肌缺血诱发心律失常及心肌缺血再灌注损伤是否具有与其他钙拮抗剂相似的保护作用未见报道。本文将对其进行探讨。     

大孔吸附树脂在提取粉防己中汉防己甲素和汉防己乙素中的应用

目的：改进粉防己中汉防己甲素、乙素的提取工艺，使其操作简便，降低提取的成本和毒性。方法：利用D101大孔吸附树脂和硅胶柱层析进行分离、提取汉防己甲素和乙素。结果：得到纯度较高的汉防己甲素和乙素，得率分别为0．06％．0．016％，纯度均大于98％。结论：利用D101大孔吸附树脂和硅胶柱层析可以有效分得汉防己甲素和乙素，且得率较高，纯度已达到标准品的要求，可用作标准品的制备。该方法与传统的分离、提取方法比较，操作简便，并且降低了成本和毒性。     

粉防己碱对获得性多药耐药小鼠S180肿瘤细胞P170,LRP,TOPO Ⅱ表达的调控

目的:观察粉防己碱口服给药对化疗诱导的多药耐药基因表达产物P₁₇₀、肺耐药蛋白LRP和拓扑异构酶Ⅱ(TOPOⅡ)的影响。方法:以亚于治疗剂量的联合化疗PFC方案,化疗诱导建立小鼠S180肿瘤细胞多药耐药模型,同时给予粉防己碱4周,流式细胞仪荧光检测P₁₇₀,LRP,TOPOⅡ。结果:粉防己碱明显降低化疗诱导后耐药细胞P₁₇₀,LRP的表达率和ROPOⅡ活性。结论:粉防己碱可通过抑制耐药基因表达和DNA拓扑异构酶活性,干预化疗诱发的肿瘤细胞多药耐药的产生。     

Inhibition of proliferation and induction of apoptosis by tetrandrine in HepG2 cells

Tetrandrine is a bisbenzylisoquinoline alkaloid derived from the root of Stephania tetrandra S. Moore, which has been reported to elicit in vitro cytotoxic effects on HeLa cells, and in vivo suppressive effects on mouse ascites tumors. In the present study, we examined the antiproliferative and apoptosis-inducing activity of tetrandrine in HepG2 cells, a human hepatoma cell line. Tetrandrine showed potent cytotoxic activity in HepG2 cells (IC(50)=9.0+/-1.0 micro M) following incubation for 48 h. Dose-dependent induction of apoptosis was observed by agarose gel electrophoresis and flow cytometric analysis. Treatment of HepG2 cells with tetrandrine resulted in the activation of caspase-3 protease, and subsequent proteolytic cleavage of poly(ADP-ribose) polymerase. These results suggest that tetrandrine is potentially useful as a chemotherapeutic/chemopreventive agent in hepatocellular carcinoma.     

粉防己碱对血小板聚集、粘附及血凝的影响

在体外实验中观测到粉防己碱可明显抑制ADP和胶原诱导的大鼠血小板聚集反应。对血小板粘附、血栓形成有明显抑制作用,而对凝血酶凝血时间、血浆凝固时间无明显影响。     

Tetrandrine and arsenic trioxide synergistically inhibit proliferation of HCC1937 triple negative breast cancer cells

OBJECTIVE: To evaluate the effects of tetrandrine plus arsenic trioxide on HCC1937 cells, a triple negative breast cancer cell line, and to explore possible mechanisms.METHODS: The 3-(4,5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide method was used to compare the antiproliferative effects of tetrandrine,arsenic trioxide alone and tetrandrine plus arsenic trioxide on HCC1937 cells. The median-effect principle(Chou-Talalay combination index method) was used to examine the interaction between the two drugs. Flow cytometry was used to evaluate effects of treatment with tetrandrine, arsenic trioxide or the combination of both on HCC1937 cell apoptosis. Real-time polymerase chain reaction and western blotting were performed to evaluate changes in apoptosis-related gene expression and protein levels.RESULTS: Tetrandrine and arsenic trioxide each in-hibited HCC1937 cell proliferation in a dose-dependent manner. The cell inhibition rate of HCC1937 cells treated with a combination of tetrandrine and arsenic trioxide was significantly higher than with either compound alone. The two drugs produced a synergistic effect when the inhibition rate was20%-40%. Flow cytometry results showed that treatment with the two drugs increased the proportion of apoptotic cells. In the combination treated group, caspase-3 activation and PARP cleavage were significantly higher than in the other groups.Moreover, Bcl-2 and survivin expression were decreased, whereas that of both Bid and Bax was increased.CONCLUSION: These findings demonstrated that tetrandrine plus arsenic trioxide had synergistic efficacy on induction of apoptosis in HCC1937 cells.     

粉防己碱对血小板聚集、粘附及血凝的影响

在体外实验中观测到粉防己碱可明显抑制ADP和胶原诱导的大鼠血小板聚集反应。对血小板粘附、血栓形成有明显抑制作用,而对凝血酶凝血时间、血浆凝固时间无明显影响。     

Tetrandrine induces apoptosis in hepatic stellate cells

We have previously reported that tetrandrine reduced hepatic stellate cell activation and collagen accumulation in liver fibrosis induced by biliary obstruction. In the present study, we examined the apoptosis-inducing effect of tetrandrine on activated hepatic stellate cells, as the therapeutic goal in hepatic fibrosis is to eliminate the activated hepatic stellate cells by apoptosis. We used rat hepatic stellate cells transformed by Simian virus 40 (T-HSC/Cl-6) to overcome the limitations inherent in studying primary cultures of hepatic stellate cells. Tetrandrine treatment at doses of 25 and 50 microg/ml for 12 h induced apoptosis as confirmed by DNA fragmentation and increased sub-G1 DNA content as detected by flow cytometric analysis. Tetrandrine also induced the activation of caspase-3 protease and subsequent proteolytic cleavage of poly(ADP-ribose) polymerase. In conclusion, our results demonstrate that tetrandrine induces apoptosis of T-HSC/Cl-6 cells, and these results should contribute to the development of new agents for the treatment of hepatic fibrosis.     

粉防己碱对小鼠吗啡诱导的高活性和强化效应的影响

目的：研究粉防己碱（Tet）对小鼠吗啡诱导的高活性和强化效应的影响。方法：单次给予吗啡用自主活动仪检测运动活性，利用位置偏爱实验评估吗啡的强化效应，用爬壁实验考察与多巴胺系统的关系，利用免疫组织化学方法显著脑内即刻早期基因c-fos的表达情况。结果：吗啡单次处理小鼠可诱导高活性，重复处理可产生位置偏爱，Tet30mg/kg或60mg/kg皮下注射可抑制吗啡诱导的高活性，60mg/kg抑制位置偏爱效应,而不影响小鼠的爬壁反应，Tet可抑制吗啡位置偏爱模型形成后伏隔核、腹侧被盖区及前额皮层c-fos阳性细胞的表达。结论：Tet能抑制吗啡诱导的高活性及强化效应，其效应可能与抑制特定脑区即刻早期 基因c-fos的表达有关。     

Inhibitory effect of tetrandrine on pulmonary metastases in CT26 colorectal adenocarcinoma-bearing BALB/c mice

Tumor metastasis is a major cause of mortality in cancer patients. The anti-metastatic effect of tetrandrine, an alkaloid isolated from Stephania tetrandrae S. Moore, was investigated in a pulmonary metastatic model of colorectal cancer-bearing mice. Tetrandrine decreased the viability of murine colorectal adenocarcinoma CT26 cells in a time- and dose-dependent manner. CT26 cells were injected into BALB/c mice via a tail vein to establish pulmonary metastases. After this, the mice were given intraperitoneal injections of tetrandrine (10 mg/kg/day), 5-fluorouracil (5-FU) at the same dose, or vehicle for 5 consecutive days. Mice treated with tetrandrine had 40.3% fewer metastases than vehicle-treated mice, and those treated with 5-FU had 36.9% fewer metastases than controls. Both tetrandrine- and 5-FU-treated mice survived longer than mice in the untreated control group. There was no acute toxicity or obvious changes in body weight in any of the mice. These results suggest that tetrandrine may be a useful anti-metastatic agent.