不同工艺提取的丹归活血制剂对博来霉素诱导的硬皮病模型小鼠皮肤和肺组织的影响  

Effects of Dangui Huoxue preparations extracted by different processes on the skin and lung tissues of bleomycin-induced systemic sclerosis mouse model

作　　者：严悦梅 杨荞榕 梁健 杨春欣 沈雄 秦万章 王强 YAN Yue-mei;YANG Qiao-rong;LIANG Jian;YANG Chun-xin;SHEN Xiong;QIN Wan-zhang;WANG Qiang(Department of Dermatology,Zhongshan Hospital,Fudan University,Shanghai 200032,China;Department of Pharmacy,Zhongshan Hospital,Fudan University,Shanghai 200032,China)

机构地区：[1]复旦大学附属中山医院皮肤科,上海200032 [2]复旦大学附属中山医院药剂科,上海200032

出　　处：《复旦学报（医学版）》2022年第3期353-359,共7页Fudan University Journal of Medical Sciences

基　　金：上海市科委生物医药领域重点项目(18401931700);上海市卫健委/上海市中医药管理局科研项目(2016ZJP001)。

摘　　要：目的观察3种不同提取工艺获得的中药新药丹归活血制剂对博来霉素诱导的硬皮病模型小鼠皮肤和肺组织的炎症与纤维化的影响。方法64只BALB/c小鼠(雌性,6周龄),背部皮肤每日皮下注射博来霉素0.1 mL,连续28天构建硬皮病模型。随机分为8组:分别为高、低剂量的工艺1(AH和AL)、2(BH和BL)、3(CH和CL)组和三七通舒胶囊阳性对照(D)组及模型(E)组,按每10 g体质量0.1 mL灌胃给药,每天1次,连续12周;另设正常对照(F)组(n=8)。末次给药后,取皮肤和肺组织进行常规病理HE染色和Masson染色、真皮厚度测量、羟脯氨酸检测。结果给药干预12周后,皮肤和肺组织均有不同程度改善。皮肤组织:AH组(0.17±0.24)、AL组(0.38±0.33)和CL组(0.75±0.25)的皮肤炎症较E组(1.33±0.47)均明显减轻(P=0.001、0.004和0.039);AL组[(188.59±16.46)μm]和AH组[(199.98±18.02)μm]的皮肤厚度较E组[(235.68±13.30)μm]均明显减少(P<0.001和P=0.006);AL组[(3024.68±654.15)μg/g]、BH组[(2948.35±1101.89)μg/g]和CL组[(2992.37±560.21)μg/g]的皮肤胶原蛋白含量较E组[(4453.26±1099.18)μg/g]均明显下降(P=0.034、0.046和0.030)。肺组织:仅有AH组(0.42±0.34)的肺部组织炎症较E组(1.33±0.47)减轻(P=0.006);BH组[(212.86±61.24)μg/g]、CH组[(229.05±86.33)μg/g]和CL组[(284.23±46.23)μg/g]的肺部组织胶原蛋白含量较E组[(349.22±49.65)μg/g]均明显下降(P=0.002、0.016和0.044)。D组皮肤和肺组织虽有改善,但差异均无统计学意义。结论不同工艺提取的丹归活血制剂能不同程度改善硬皮病模型小鼠的皮肤和肺部组织的炎症与纤维化病变,其中以工艺1(水煎酒沉法)疗效最佳,高剂量组中肺改善略好,低剂量组中皮肤改善更佳。Objective To explore the effects of Dangui Huoxue preparations obtained by three different extraction processes on the inflammation and fibrosis of skin and lung tissues in the bleomycin(BLM)-induced mouse model of systemic sclerosis(SSc).Methods Sixty-four female BALB/c mice of 6 weeks old were injected subcutaneously with 0.1 mL of bleomycin daily on the back skin for 28 consecutive days to construct a SSc mouse model and then randomly divided into 8 groups:high and low doses of process 1(AH and AL),process 2(BH and BL),process 3(CH and CL)and positive control(D)group of Sanqi Tongshu capsule and SSc wild-type(E)group.According to 0.1 mL/10 g body weight,different groups of mice were given different drugs at different doses by gavage respectively for 12 consecutive weeks.Another 8 BALB/c mice were set as normal control(F)group.After the last administration,the tissues of skin and lung from all mice were taken for routine detections of pathology including HE staining and Masson staining,dermal thickness measurement,and hydroxyproline(HYP)detection.Results After 12 weeks of administration,there were some improvements in the skin and lung tissues.The skin inflammation was reduced in AH group(0.17±0.24),AL group(0.38±0.33)and CL group(0.75±0.25)compared with E group(1.33±0.47)(P=0.001,0.004 and 0.039,respectively).The dermal thickness was reduced in AL group[(188.59±16.46)μm]and AH group[(199.98±18.02)μm]compared with E group[(235.68±13.30)μm](P<0.001 and P=0.006,respectively).The skin collagen content was reduced in AL group[(3024.68±654.15)μg/g],BH group[(2948.35±1101.89)μg/g]and CL group[(2992.37±560.21)μg/g]compared with E group[(4453.26±1099.18)μg/g](P=0.034,0.046 and 0.030,respectively).The inflammation of lung tissues was reduced in AH group(0.42±0.34)compared with E group(1.33±0.47)(P=0.006).The collagen content of lung tissues was reduced in BH group[(212.86±61.24)μg/g],CH group[(229.05±86.33)μg/g]and CL group[(284.23±46.23)μg/g]compared with E group[(349.22±49.65)μg/g](P=0.002,

关 键 词：丹归活血制剂 硬皮病 病理 羟脯氨酸检测 小鼠 

分 类 号：R593.25[医药卫生—内科学]