Xing C, Yang Z F, Bo C X, Tang Q, Jia Q, Zhang Z L, Shao H
Shandong First Medical University (Shandong Academy of Medical Sciences), Shandong Academy of Occupational Health and Occupational Medicine, Jinan 250062, China.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2022 Jan 20;40(1):12-17. doi: 10.3760/cma.j.cn121094-20210420-00218.
To investigate the effect of asiaticoside for fibrosis in lung tissues of rats exposed to silica and to explore its possible mechanism. 144 SD male rats were randomly divided into control group, model group, positive drug control group, asiaticoside high-dose group, medium-dose group and low-dose group, each group included 24 rats. Rats in the control group were perfused with 1.0 ml of normal saline, and the other groups were given 1.0 ml 50 mg/ml SiO(2) suspension. Gavage of herbal was given from the next day after model establishment, once a day. Rats in the positive drug control group were administration with 30 mg/kg tetrandrine and rats in the low-dose group, medium-dose group and high-dose group were given 20 mg/kg, 40 mg/kg and 60 mg/kg asiaticoside for fibrosis respectively. Rats in the control group and the model group were given 0.9% normal saline. The rats were sacrificed in on the 14th, 28th and 56th day after intragastric administration and collect the lung tissues to detect the content of hydroxyproline, TGF-β(1) and IL-18, observe the pathological changes of the lung tissues by HE and Masson staining and determine the expressions of Col-I, a-SMA, TGF-β in lung tissues by Western Blot. On the 14th day, 28th day and 56th day after model establishment, the lung tissues of rats in the model group showed obvious inflammatory response and accumulation of collagen fibers, and the degree of inflammation and fibrosis increased with time. The intervention of asiaticoside could effectively inhibit the pathological changes of lung tissues. The contents of hydroxyproline, IL-18 and TGF-β1 in lung tissues of model group were higher than those in the control group (<0.05) , while the level of hydroxyproline, IL-18 and TGF-β1 in asiaticoside groups were significantly decreased, and the difference was statistically signicant (<0.05) . Compared with the control group, the expression levels of Col-I, TGF-β1and α-SMA in lung tissue of model group were increased (<0.05) , while the expression level of Col-I, TGF-β1 and α-SMA were decreased after the intervention of asiaticoside, and the difference was statistically signicant (<0.05) . Asiaticoside can inhibit the increase of Col-I, TGF-β1 and α-SMA content in the SiO(2)-induced lung tissues of rats, reduce the release of TGF-β1 and IL-18 inflammatory factors in lung tissue, and then inhibit the synthesis and deposition of extracellular matrix in rat lung tissue, and improve silicosis fibrosis.
探讨积雪草苷对二氧化硅暴露大鼠肺组织纤维化的影响并探究其可能机制。将144只雄性SD大鼠随机分为对照组、模型组、阳性药物对照组、积雪草苷高剂量组、中剂量组和低剂量组,每组24只。对照组大鼠灌胃1.0 ml生理盐水,其他组大鼠给予1.0 ml 50 mg/ml SiO₂混悬液。造模次日开始灌胃给药,每日1次。阳性药物对照组大鼠给予30 mg/kg汉防己甲素,低剂量组、中剂量组和高剂量组大鼠分别给予20 mg/kg、40 mg/kg和60 mg/kg积雪草苷用于抗纤维化。对照组和模型组大鼠给予0.9%生理盐水。在灌胃给药后第14天、28天和56天处死大鼠,采集肺组织检测羟脯氨酸、转化生长因子-β1(TGF-β1)和白细胞介素-18(IL-18)含量,通过苏木精-伊红(HE)和马松(Masson)染色观察肺组织病理变化,并用蛋白质免疫印迹法检测肺组织中I型胶原(Col-I)、α-平滑肌肌动蛋白(α-SMA)、TGF-β的表达。造模后第14天、28天和56天,模型组大鼠肺组织出现明显炎症反应及胶原纤维堆积,且炎症和纤维化程度随时间加重。积雪草苷干预可有效抑制肺组织病理改变。模型组肺组织中羟脯氨酸、IL-18和TGF-β1含量高于对照组(P<0.05),而积雪草苷各剂量组羟脯氨酸、IL-18和TGF-β1水平均显著降低,差异有统计学意义(P<0.05)。与对照组相比,模型组肺组织中Col-I、TGF-β1和α-SMA表达水平升高(P<0.05),积雪草苷干预后Col-I、TGF-β1和α-SMA表达水平降低,差异有统计学意义(P<0.05)。积雪草苷可抑制二氧化硅诱导的大鼠肺组织中Col-I、TGF-β1和α-SMA含量增加,减少肺组织中TGF-β1和IL-18炎性因子释放,进而抑制大鼠肺组织细胞外基质的合成与沉积,改善矽肺纤维化。