Bleomycin hydrochloride 是一种抑制 DNA 合成的 DNA 损伤剂，并且是一种抗肿瘤抗生素。博来霉素是治疗恶性肿瘤的常用药物，在硬皮病的发病中起主要作用，能促进来自皮肤成纤维细胞的Ⅰ型胶原、Ⅲ型胶原纤维粘连蛋白等细胞外基质的基因转录及蛋白合成，且能抑制细胞外基质分解酶的活性。
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Bleomycin hydrochloride is a DNA synthesis inhibitor. Bleomycin hydrochloride is a DNA damaging agent. Bleomycin hydrochloride is an antitumor antibiotic[1].
体内研究
In animal models, Bleomycin hydrochloride is used to construct pulmonary fibrosis models, demonstrating its capability to cause significant lung damage and fibrosis. Administered intratracheally at doses ranging from 3.5 to 4.0 mg/kg, it leads to a decrease in body weight by day 4, followed by a recovery in weight from day 7 onwards. This treatment also significantly increases lung hydroxyproline levels and the mass of the right caudal lung lobe, indicative of fibrosis[3].
Additionally, intratracheal instillation of Bleomycin at 5.0 mg/kg/day in male BALB/c mice induces pulmonary fibrosis, elevating the expression levels of α-SMA and collagen I, markers of fibrotic response[4].
A similar fibrotic response is observed in male C57BL/6 mice with a dose of 2.5 mg/kg, further validating its utility in modeling pulmonary fibrosis[5].
体外研究
Bleomycin hydrochloride's mechanism of action includes the induction of single and double-strand breaks as well as apurinic/apyrimidinic sites within DNA, making it a potent genotoxic compound. Its effects are comparable to those of ionizing radiation, making it a radiomimetic compound. It has been extensively studied for its ability to induce micronuclei in human lymphocytes, a marker of genotoxic stress[1].
In terms of its efficacy against cancer cell lines, Bleomycin hydrochloride exhibits a relatively low IC50 value of 4.0±1.3 nM against the UT-SCC-19A cell line, demonstrating its potent cytotoxic effect. In contrast, the UT-SCC-12A and UT-SCC-12B cell lines show higher resistance to Bleomycin, with IC50 values of 14.2±2.8 nM and 13.0±1.1 nM, respectively[2].
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