It was previously thought that the Panton-Valentine leukocidin (PVL) toxin of Staphylococcus aureus (S. aureus) was not the main cause of cow mastitis. However, in recent years, detection of the gene encoding PVL has been increasing in dairy cow mastitis, which implies that PVL may be related to bovine mastitis. Therefore, we wanted to search for drugs inhibiting PVL or PVL-induced apoptosis. In this report, we investigated the apoptosis mechanism of PVL in bovine mammary epithelial cells (BMEC) and the inhibition mechanism of matrine and baicalin on PVL-induced apoptosis of BMEC. The results demonstrated that BMEC were damaged and underwent apoptosis by a standard PVL-producing strain of S. aureus (ATCC 49775), a PVL knockout mutant Δpvl 49775, complemented mutant C-Δpvl 49775, or recombinant (r)PVL in vitro. The rates of apoptosis and necrosis induced by S. aureus ATCC 49775 and C-Δpvl 49775 were significantly higher than those induced by Δpvl 49775, demonstrating that BMEC apoptosis and necrosis were associated with PVL. In addition, this research found matrine and baicalin could inhibit the apoptosis of BMEC induced by PVL-producing S. aureus and by rPVL. Matrine downregulated protein expression levels of endogenous and exogenous cleaved caspase-3, cleaved caspase-8, and cleaved caspase-9, and the effect was pronounced at a concentration of 50 μg/mL. Baicalin downregulated the expression of cleaved caspase-9. These results suggested that matrine and baicalin may have potential value against cow mastitis caused by the toxin PVL.

中文翻译：

---

苦参碱和黄ical苷抑制牛乳腺上皮细胞中金黄色葡萄球菌潘通-华伦特白介素诱导的凋亡。

以前认为，金黄色葡萄球菌（S. aureus）的Panton-Valentine leukocidin（PVL）毒素不是牛乳腺炎的主要原因。然而，近年来，在乳牛乳腺炎中编码PVL的基因的检测一直在增加，这暗示PVL可能与牛乳腺炎有关。因此，我们想寻找抑制PVL或PVL诱导的细胞凋亡的药物。在本报告中，我们研究了PVL在牛乳腺上皮细胞（BMEC）中的凋亡机制以及苦参碱和黄ical苷对PVL诱导的BMEC凋亡的抑制机制。结果表明，BMEC被标准的产生PVL的金黄色葡萄球菌（ATCC 49775），PVL敲除突变体Δpvl49775，互补突变体C-Δpvl49775或重组（r）PVL损伤并经历了凋亡。金黄色葡萄球菌ATCC 49775和C-Δpvl49775诱导的细胞凋亡和坏死率显着高于Δpvl49775诱导的细胞凋亡和坏死率，表明BMEC细胞凋亡和坏死与PVL相关。另外，该研究发现苦参碱和黄ical苷可以抑制由产生PVL的金黄色葡萄球菌和rPVL诱导的BMEC的凋亡。苦参碱下调了内源性和外源性裂解的caspase-3，裂解的caspase-8和裂解的caspase-9的蛋白质表达水平，并且在50μg/ mL的浓度下效果显着。黄ical素下调切割的caspase-9的表达。这些结果表明苦参碱和黄ical苷可能对由毒素PVL引起的奶牛乳腺炎具有潜在价值。表明BMEC凋亡和坏死与PVL有关。另外，该研究发现苦参碱和黄ical苷可以抑制由产生PVL的金黄色葡萄球菌和rPVL诱导的BMEC的凋亡。苦参碱下调了内源性和外源性裂解的caspase-3，裂解的caspase-8和裂解的caspase-9的蛋白质表达水平，并且在50μg/ mL的浓度下效果显着。黄ical素下调切割的caspase-9的表达。这些结果表明苦参碱和黄ical苷可能对由毒素PVL引起的奶牛乳腺炎具有潜在价值。表明BMEC凋亡和坏死与PVL有关。另外，该研究发现苦参碱和黄ical苷可以抑制由产生PVL的金黄色葡萄球菌和rPVL诱导的BMEC的凋亡。苦参碱下调了内源性和外源性裂解的caspase-3，裂解的caspase-8和裂解的caspase-9的蛋白质表达水平，并且在50μg/ mL的浓度下效果显着。黄ical素下调切割的caspase-9的表达。这些结果表明苦参碱和黄ical苷可能对由毒素PVL引起的奶牛乳腺炎具有潜在价值。苦参碱下调了内源性和外源性裂解的caspase-3，裂解的caspase-8和裂解的caspase-9的蛋白质表达水平，并且在50μg/ mL的浓度下效果显着。黄ical素下调切割的caspase-9的表达。这些结果表明苦参碱和黄ical苷可能对由毒素PVL引起的奶牛乳腺炎具有潜在价值。苦参碱下调了内源性和外源性裂解的caspase-3，裂解的caspase-8和裂解的caspase-9的蛋白质表达水平，并且在50μg/ mL的浓度下效果显着。黄ical素下调切割的caspase-9的表达。这些结果表明苦参碱和黄ical苷可能对由毒素PVL引起的奶牛乳腺炎具有潜在价值。