丹参单体IH764-3通过激活半胱天冬酶-3诱导肝星状细胞凋亡。
Salvia miltiorrhiza monomer IH764-3 induces hepatic stellate cell apoptosis via caspase-3 activation.
作者信息
Zhang Xiao-Lan, Liu Li, Jiang Hui-Qing
机构信息
Department of Gastroenterology The Second Hospital of Hebei Medical University Shijiazhuang 050000 Hebei Province China.
出版信息
World J Gastroenterol. 2002 Jun;8(3):515-9. doi: 10.3748/wjg.v8.i3.515.
AIM
To investigate the effects of IH764-3 on HSC apoptosis and the expression of caspase-3 protein in HSC apoptotic process.
METHODS
HSCs were cultured in medium with different IH764-3 doses(10 microg.mL(-1) 20 microg.mL(-1) 30 microg.mL(-1) 40 microg.mL(-1)) and without IH764-3 and HSC proliferation was quantitatively measured by (3)H-thymidine incorporation. The morphological changes of HSCs were observed with transmission electron microscope after exposure to the dose of 40 microg.mL(-1) of IH764-3 for 48 hr. The apoptosis rates were detected by annexin V/PI and TdT-mediated dUTP nick end labeling (TUNEL). The expression of caspase-3 protein was determined by flow cytometry.
RESULTS
(1) HSC proliferation rates induced with different IH764-3 doses (10 microg.mL(-1) 20 microg.mL(-1) 30 microg.mL(-1) 40 microg.mL(-1)) were significantly reduced compared with that of the control group (P<0.01). (2)With the doses above,IH764-3 dose-dependently produced HSC apoptosis rates of 6.7%(9.4%) 9.3%(21.6%) 15.1%(27.2%) and 19.0%(28.4%) respectively by annexin V and PI-labeled flow cytometry assay or TUNEL while it was only 2.3%(6.7%) in the control. (3) The expression of caspase-3 protein in IH764-3 groups was significantly higher than that of the control (P<0.05).
CONCLUSION
Within the dose range used in present study IH764-3 can inhibit HSC proliferation as well as enhance HSC apoptosis. Furthermore IH764-3 can significantly increase the caspase-3 protein expression.
目的
研究IH764 - 3对肝星状细胞（HSC）凋亡及HSC凋亡过程中半胱天冬酶 - 3蛋白表达的影响。
方法
将HSC培养于含不同剂量IH764 - 3（10μg·mL⁻¹、20μg·mL⁻¹、30μg·mL⁻¹、40μg·mL⁻¹）及不含IH764 - 3的培养基中，通过³H - 胸腺嘧啶核苷掺入法定量检测HSC增殖。在暴露于40μg·mL⁻¹的IH764 - 3 48小时后，用透射电子显微镜观察HSC的形态变化。通过膜联蛋白V/碘化丙啶（PI）和末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法（TUNEL）检测凋亡率。用流式细胞术测定半胱天冬酶 - 3蛋白的表达。
结果
（1）与对照组相比，不同剂量（10μg·mL⁻¹、20μg·mL⁻¹、30μg·mL⁻¹、40μg·mL⁻¹）的IH764 - 3诱导的HSC增殖率显著降低（P<0.01）。（2）上述剂量下，通过膜联蛋白V和PI标记的流式细胞术检测或TUNEL法，IH764 - 3分别剂量依赖性地使HSC凋亡率达到6.7%（9.4%）、9.3%（21.6%）、15.1%（27.2%）和19.0%（28.4%），而对照组仅为2.3%（6.7%）。（3）IH764 - 3组中半胱天冬酶 - 3蛋白的表达显著高于对照组（P<0.05）。
结论
在本研究使用的剂量范围内，IH764 - 3可抑制HSC增殖并增强HSC凋亡。此外，IH764 - 3可显著增加半胱天冬酶 - 3蛋白的表达。
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