丹参酮Ⅱ A 磺酸钠对血管紧张素Ⅱ诱导的大鼠心肌纤维化的影响

Sodium Tanshinone A Sulfonate attenuates angiotensin -induced cardiac fibrosis in rats

摘要:

目的 观察丹参酮Ⅱ A 磺酸钠（STS）对血管紧张素Ⅱ（Ang Ⅱ）诱导的大鼠心肌纤维化的影响； 并初步探讨STS 抗心肌纤维化的作用与转录因子NF-E2 相关因子2（Nrf2）所调控的抗氧化应激反应的关系。 方法 40 只SD 大鼠随机分为5 组（对照组，模型组，低、中、高剂量STS 组），采用皮下植入微量渗透泵缓释 Ang Ⅱ复制大鼠心肌纤维化模型，各STS 组给予不同剂量STS 处理。3 周后，采用苏木精伊红和马松染色法 观察心肌纤维化程度；采用qRT-PCR 和Western blot 检测心肌组织中Ⅰ、Ⅲ型胶原，Nrf2 和它的胞质接头 蛋白Keap1，以及Nrf2 所调控的抗氧化酶和Ⅱ相解毒酶mRNA 水平及其蛋白水平；采用比色法检测心肌组 织中丙二醛、谷胱甘肽水平及超氧化物歧化酶活性。结果 STS 呈剂量依赖性地减轻Ang Ⅱ诱导的心肌纤维化， 促使Nrf2 在细胞核内的聚集，提高抗氧化酶及Ⅱ相解毒酶的表达，增强抗氧化应激反应，降低心肌组织脂质过 氧化水平。结论 STS 能够有效减轻Ang Ⅱ诱导的大鼠心肌纤维化，其抗纤维化作用与调控Nrf2 信号通路相关。

Abstract:

Objective To investigate the effect of Sodium Tanshinone IIA Sulfonate (STS) on angiotensin II (Ang II) -induced cardiac fibrosis in rats and potential mechanisms. Methods Rat model of cardiac fibrosis was established through constant introduction of Ang II delivered byosmotic pump.Totally 40 male Sprague-Dawley rats were randomly divided into control group, Ang II group, low-dose STS group, medium-dose STS group and highdose STS group. STS were administered for three consecutive weeks. H&E and Masson’s trichrome staining were performedfor morphological analysis. Expression levels of Keap1, Nrf2, Collagen I & III, antioxidant enzymes and phase II enzymes were examined with qRT-PCR and Western blot. Malondialdehyde, glutathioneand superoxide dismutase activity in cardiac tissues were identified. Results STS treatment attenuated Ang II-induced cardiac fibrosis. STS stimulatednuclear translocation of Nrf2 in a dose-dependent manner, promoting the transcription of antioxidant and phase II enzymes. Enhanced anti-oxidative activities contributed to cellular protection against oxidative stress. Conclusion STS attenuates Ang II-induced cardiac fibrosis by manipulating Nrf2 mediated antioxidation signaling pathway.