丹参酮ⅡA磺酸钠对大鼠矽肺早期的干预作用

Intervention effect of sodium tanshinone ⅡA sulfonate on early-stage silicosis in rats

[目的]探讨丹参酮ⅡA磺酸钠对大鼠矽肺早期的治疗作用。[方法] SPF级成年SD雄性大鼠96只随机分为正常对照组、药物对照组、动式染尘组及药物治疗组,每组分别在7、14、28、56 d等不同时间点处死大鼠,每组6只。动式染尘组给予动式吸入染尘;药物治疗组除每天给予动式染尘外,腹腔注射丹参酮ⅡA磺酸钠15 mg/(kg·d);药物对照组给予等剂量丹参酮ⅡA磺酸钠;正常对照组不做处理。苏木素-伊红(HE)染色观察肺组织病变情况;利用淋巴管透明质酸受体1(LYVE-1)标记淋巴管,采用免疫组化法检测肺组织内淋巴管增生情况;采用试剂盒检测大鼠淋巴液内丙二醛(MDA)、酶联免疫吸附试验检测血清中层粘连蛋白(LN)的表达水平;Western blot检测大鼠肺组织内单核细胞趋化蛋白1(MCP-1)的表达。[结果] HE染色结果显示,药物治疗组大鼠病变程度较动式染尘组有所减轻。与正常对照组相比,动式染尘组大鼠的淋巴液中MDA含量和LYVE-1标记的阳性淋巴管数量在染尘14 d时均达到高峰[(10.61±0.56)μg/L、4.50(4.00～5.00)];动式染尘组大鼠肺组织中MCP-1和血清中LN的水平在56 d时分别为1.84±0.01、(456.73±10.01)μg/L。与处理56 d的动式染尘组相比,药物治疗组大鼠淋巴液中MDA[(5.69±0.90)μg/L]、肺组织中MCP-1(1.45±0.07)以及血清中LN[(427.43±13.89)μg/L]的表达有所降低。[结论]丹参酮ⅡA磺酸钠注射液通过改善矽肺大鼠肺内淋巴微循环、氧化应激以及炎症反应延缓矽肺大鼠发病进程。

[Objective] To assess the therapeutic effect of sodium tanshinone ⅡA sulfonate on early-stage silicosis in rats.[Methods] Ninety-six adult male SD rats of SPF grade were randomly divided into normal control group, drug control group, dynamic dust exposure group, and drug treatment group, and sacrificed at designed time points(7 d, 14 d, 28 d, and 56 d), with six rats in each subgroup. The dust exposure group was given dynamic inhalation of silica dust;the drug treatment group received intraperitoneal injection of sodium tanshinone ⅡA sulfonate at 15 mg/(kg·d) in addition to dust exposure everyday;the drug control group was only given an equal dose of sodium tanshinone ⅡA sulfonate;the normal control group received neither dust exposure nor designed treatment. The pathological changes of lung tissues were observed by hematoxylin-eosin(HE) staining;lymphatic hyperplasia in lung tissues was detected by immunohistochemistry after lymphatic vessels being labeled with hyaluronic acid receptor 1(LYVE-1);malondialdehyde(MDA) in rat lymph was assessed by biochemical kit;laminin(LN) in serum was evaluated by enzymelinked immunosorbent assay;and the expression of monocyte chemotactic protein-1(MCP-1) in rat lung tissues was detected by Western blot.[Results] The HE staining results showed that the pathological changes in the rats of the drug treatment group were relieved compared with those of the dynamic dust exposure group.Compared with the normal control group, the MDA content and LYVE-1 labeled positive lymphatic vessels in lymph of rats exposed to dynamic dust reached the peak at 14 d [(10.61±0.56)μg/L, 4.50(4.00-5.00)];the levels of MCP-1 in lung tissues and LN in serum of rats exposed to dynamic dust were 1.84±0.01 and(456.73±10.01)μg/L at 56 d. Compared with the dynamic dust exposure group at 56 d, the levels of MDA in lymph [(5.69±0.90)μg/L], MCP-1 in lung tissues(1.45±0.07), and LN in serum [(427.43±13.89)μg/L] of the drug treatment group were decreased.[Conclusion] Sodium tanshinone ⅡA sulfonate injection may delay the pathogenesis of silicosis in rats by improving the microcirculation of lung lymph, oxidative stress, and inflammatory reaction.