鹿龙再生汤Ⅱ号方对化疗后骨髓抑制的作用机制  

Effect of Lulong Zaisheng DecoctionⅡon chemotherapy-induced bone marrow suppression and its mechanism

作　　者：崔伟伟[1,2] 彭飞[1,2] 秦婷婷[1,2] 胡灿红 郁兆婧 方志军[1,2] 朱建华 CUI Wei-wei;PENG Fei;QIN Ting-ting;HU Can-hong;YU Zhao-jing;FANG Zhi-jun;ZHU Jian-hua(Affiliated Hospital of Integrated Traditional Chinese and Western Medicine,Nanjing University of Chinese Medicine,Nanjing 210028,China;Jiangsu Province Academy of Traditional Chinese Medicine,Nanjing 210028,China;Liang-chun Guoyitang of Nantong,Nantong,Jiangsu 226001,China;Affiliated Hospital of Nantong University,Nantong,Jiangsu 226001,China)

机构地区：[1]南京中医药大学附属中西医结合医院,江苏南京210028 [2]江苏省中医药研究院,江苏南京210028 [3]南通良春国医堂,江苏南通226001 [4]南通大学附属医院,江苏南通226001

出　　处：《中国药理学通报》2023年第5期986-993,共8页Chinese Pharmacological Bulletin

基　　金：江苏省重点研发计划(社会发展)专项(No BE2021753);江苏省中医药研究院自主科研项目重点项目(No BM2018024-2019005)。

摘　　要：目的探讨鹿龙再生汤Ⅱ号方对荷瘤裸鼠骨髓抑制的干预作用机制。方法肠癌荷瘤裸鼠随机分为5组:对照组、化疗组、化疗加利可君片组,化疗加鹿龙再生汤Ⅱ号方高、低剂量组,连续灌胃给药10 d。d 4-10,除对照组外,均腹腔注射氟尿嘧啶(5-Fu)25 mg·kg^(-1)。d 11检测外周血白细胞、骨髓有核细胞数,流式细胞仪检测骨髓细胞周期、凋亡率及CD34阳性率,荧光定量PCR检测骨髓粒细胞巨噬细胞集落刺激因子(granulocyte-macrophage colony stimulating factor,GM-CSF)、粒细胞巨噬细胞刺激因子受体(granulocyte-macrophage colony stimulating factor receptor,GM-CSFR)以及淋巴细胞刺激因子白细胞介素1β(interleukin-1β,IL-1β)、白细胞介素3(interleukin-3,IL-3)的mRNA水平,Western blot考查血管内皮生长因子(vascular endothelial growth factor,VEGF)和血管细胞黏附分子-1(intercellular cell adhesion molecule-1,VCAM-1)的表达。结果鹿龙再生汤Ⅱ号方能明显升高荷瘤化疗裸鼠的外周血白细胞及骨髓有核细胞数、增加骨髓细胞S期百分率、降低凋亡率并升高CD34阳性率,上调GM-CSF、GM-CSFR、IL-1β以及IL-3的mRNA表达,升高VEGF和VCAM-1蛋白水平。结论鹿龙再生汤Ⅱ号方可明显缓解化疗所致骨髓抑制,其机制与调控细胞周期、阻止细胞凋亡、促进造血生长因子的分泌以及改善骨髓造血微环境等密切相关。Aim To investigate the effect of Lulong Zaisheng DecoctionⅡon chemotherapy-induced bone marrow suppression in nude mice bearing colorectal cancer.Methods Male BALB/C nude mice were inoculated with human colon cancer cell HT-29 under the armpit.The tumor bearing nude mice were randomly divided into five groups:control group,chemotherapy group,positive drug group,Lulong Zaisheng DecoctionⅡgroups with high and low doses.The mice were given drugs by gavage once a day for 10 consecutive days.From the fourth day of the experiment,except for the control group,the nude mice were intraperitoneally injected with 5-FU at dose of 25 mg·kg^(-1)for 7 consecutive days.The mice in control group were injected with the same volume of normal saline.On the 11th day,blood was collected from the orbit to measure peripheral hemogram.The mice were killed after cervical dislocation,then the morphology of bone marrow cells was observed.Bone marrow cell cycle,apoptosis rate and CD34+were detected by flow cytometry,mRNA expressions of granulocyte-macrophage colony stimulating factor(GM-CSF),granulocyte-macrophage colony stimulating factor receptor(GM-CSFR),interleukin-1β(IL-1β)and interleukin-3(IL-3)were tested by quantitative real-time PCR,and the protein expressions of vascular endothelial growth factor(VEGF)and intercellular cell adhesion molecule-1(VCAM-1)were tested by Western blot.Results Lulong Zaisheng DecoctionⅡsignificantly elevated the number of white cells,increased the proportion of CD34 positive cells and the percentage of S cells,and reduced the apoptosis rate of bone marrow cells.Furthermore,it obviously up-regulated the mRNA expressions of GM-CSF,GM-CSFR,IL-1βand IL-3,and promoted the protein expressions of VEGF and VCAM-1 in bones.Conclusions Lulong Zaisheng DecoctionⅡcan significantly alleviate bone marrow suppression caused by chemotherapy.Its mechanism is closely related to regulating cell cycle,preventing bone marrow cell apoptosis,promoting the secretion and expression of hematopoietic growth factors,and i

关 键 词：鹿龙再生汤Ⅱ号方 肠癌 化疗 骨髓抑制 凋亡 细胞周期 

分 类 号：R-332[医药卫生] R289.5R322.2R329.25R735.3