姜黄素通过抑制凋亡信号调节激酶1减弱PM2.5短期暴露致大鼠子宫损伤

细颗粒物(PM2.5)是空气动力学直径 ≤ 2.5 μm的颗粒物，能诱发多种疾病。已有大量的流行病学调查证实，PM2.5能够损伤生殖系统，但其致病机制不明确，相关的研究也非常有限。为研究PM2.5短期暴露对大鼠子宫的损伤，以及姜黄素（curcumin, CRC）对其保护作用，本研究将50只雌性SD大鼠随机分为生理盐水对照组、PM2.5暴露组、低剂量姜黄素组（PM2.5+CRC-L）、高剂量姜黄素组（PM2.5+CRC-H）和维生素E干预组（PM2.5+VE），连续暴露30 d。经PM2.5短期暴露，暴露组雌鼠子宫内膜上皮细胞萎缩，组织结构模糊，内膜腺体细胞和基质细胞排列混乱。给予姜黄素和VE后，子宫内膜损伤明显降低。TUNEL检测凋亡结果显示，PM2.5暴露组子宫组织细胞凋亡率 (48.81±8.27)%明显高于对照组凋亡率（P<0.05）。与PM2.5暴露组相比，姜黄素能降低PM2.5诱发的子宫细胞凋亡，且PM2.5+CRC-H组细胞凋亡率(20.79±3.63)%明显低于暴露组（P<0.05）。与对照组相比，PM2.5暴露组子宫组织活性氧（ROS）含量明显升高（P<0.05），总抗氧化能力（T-AOC）含量明显降低（P<0.05）；给予姜黄素和VE，能不同程度地缓解子宫氧化应激反应。Western印迹结果显示，与PM2.5暴露组相比，姜黄素和VE能够明显抑制因PM2.5暴露诱导的凋亡信号调节激酶1(ASK1)、c-Jun氨基末端激酶(JNK)、p38 蛋白激酶(p38)磷酸化，以及胱天蛋白酶-3（caspase-3）的活化 (P<0.05)。由此可见，姜黄素能够明显减轻PM2.5短期暴露诱发的子宫损伤，这可能与其抑制ASK1介导的JNK-p38-caspase-3细胞凋亡信号通路有关。

Curcumin Attenuates Uterine Injury Induced by Short-term PM2.5 Exposure in Rats by Inhibiting Apoptosis Signal Regulating Kinase 1

Fine particulate matter (PM2.5) with diameters of less than 2.5 µm can lead to many diseases in human. According to the results of epidemiological studies, PM2.5 can injury human reproductive system, but the mechanism of reproductive injury is rarely reported. This study aimed to investigate the protective effect and mechanism of curcumin (CRC) on short-term exposure to PM2.5-induced rat uterine injury. Fifty Sprague-Dawley rats were randomly divided into control group, PM2.5 exposure group, PM2.5+CRC-L group, PM2.5+CRC-H group and PM2.5+VE group, which all were administered for 30 days. After a short-term exposure, PM2.5 induced atrophy of endometrial epithelial cells and structural damage of endometrial glands and stromal cells. At the same time, these conditions were improved after administered with curcumin and VE. The results of TUNEL detection showed that the cell apoptosis rate (48.81±8.27)% in PM2.5 exposure group was significantly higher than that in control group (P<0.05). Compared to PM2.5 exposure group, the uterine cell apoptosis rates in two curcumin groups were attenuated, and the cell apoptosis rate was significantly decreased in PM2.5+CRC-H group (P<0.05). Compared to control group, the levels of reactive oxygen species (ROS) were significantly higher (P<0.05) and the level of total antioxidant capacity (T-AOC) was significantly lower (P<0.05) in PM2.5 exposure group. However, curcumin and VE could attenuate PM2.5- induced oxidative stress in rat uterus. CRC and VE inhibited proteins phosphorylation of ASK1, JNK, p38 and activation of caspase-3 induced by PM2.5 (P<0.05). Moreover, curcumin significantly inhibited the protein expression levels of p-ASK1, p-JNK, p-p38 and cleaved caspase-3 induced by PM2.5. In conclusion, curcumin attenuates short-term exposure to PM2.5-induced uterine injury by inhibiting the signal pathway of JNK-p38-caspase-3 mediated by ASK1.