地肤通乳散治疗奶牛乳房炎临床疗效及作用靶点预测
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摘要
为探讨地肤通乳散治疗奶牛乳房炎的临床效果、抗菌活性及作用机制,先利用微量肉汤法测定地肤通乳散对奶牛乳房炎主要病原菌体外抗菌活性,再对患有乳房炎的奶牛进行治疗,观察治愈率和有效率,最后利用BATMAN、STRING、Cytoscape等数据库及软件对地肤通乳散治疗奶牛乳房炎作用靶点进行分析。结果显示,地肤通乳散对无乳链球菌抑制、杀灭浓度均为1.52 mg·mL~(-1);对大肠埃希菌和金黄色葡萄球菌的最小抑制浓度为25 mg·mL~(-1),最小杀菌浓度是最小抑制浓度的2倍;对奶牛乳房炎的治愈率为63.16%,有效率可达89.47%。地肤通乳散中共筛选得到21个活性化合物,对应靶点173个,枢纽靶点5个。上述结果说明,地肤通乳散对奶牛乳房炎主要病原菌体外抗菌活性较高,临床疗效确切,可能主要通过枢纽靶点5′-核苷酸酶、白介素-8、雌激素受体1、磷脂酰肌醇-4,5-二磷酸3-激酶催化亚基α和磷脂酰肌醇-4,5-二磷酸3-激酶催化亚基β作用于肿瘤坏死因子、Janus激酶2、Toll样受体4、原癌基因RelA、NF-κB亚基和趋化因子CXCL12来治疗奶牛乳房炎。
To study the antibacterial activity, clinical effect and mechanism of Difutongrusan in the treatment of bovine mastitis. The antibacterial activities of Difutongrusan against the main pathogens of bovine mastitis were determined by the method of micro broth first, then the cows with mastitis were treated to observe the cure rate and the effective rate. Finally, BATMAN, STRING, Cytoscape databases and softwares were used to analyze the mechanism of treatment of bovine mastitis by Difutongrusan. The results showed that the MIC/MBC of Difutongrusan on Staphylococcus agalactiae was 1.52 mg·mL~(-1), the MIC on Escherichia coli and Staphylococcus aureus was 25 mg·mL~(-1), and the MBC was twice as high as the MIC; The clinical cure rate of bovine mastitis was 63.16% and the effective rate was 89.47%. A total of 21 active compounds were selected from Difutongrusan, with 173 corresponding targets and 5 pivotal targets. The results indicated that Difutongrusan could have high antibacterial activity in vitro against the main pathogenic bacteria of bovine mastitis, and the clinical efficacy could be definite, which may be mainly through the pivotal target NT5 E, IL8, ESR1, PIK3 CA and PIK3 CB to treat bovine mastitis.
To study the antibacterial activity, clinical effect and mechanism of Difutongrusan in the treatment of bovine mastitis. The antibacterial activities of Difutongrusan against the main pathogens of bovine mastitis were determined by the method of micro broth first, then the cows with mastitis were treated to observe the cure rate and the effective rate. Finally, BATMAN, STRING, Cytoscape databases and softwares were used to analyze the mechanism of treatment of bovine mastitis by Difutongrusan. The results showed that the MIC/MBC of Difutongrusan on Staphylococcus agalactiae was 1.52 mg·mL~(-1), the MIC on Escherichia coli and Staphylococcus aureus was 25 mg·mL~(-1), and the MBC was twice as high as the MIC; The clinical cure rate of bovine mastitis was 63.16% and the effective rate was 89.47%. A total of 21 active compounds were selected from Difutongrusan, with 173 corresponding targets and 5 pivotal targets. The results indicated that Difutongrusan could have high antibacterial activity in vitro against the main pathogenic bacteria of bovine mastitis, and the clinical efficacy could be definite, which may be mainly through the pivotal target NT5 E, IL8, ESR1, PIK3 CA and PIK3 CB to treat bovine mastitis.
引文
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[10] 白东东,李新圃,杨峰,等.基于网络药理学分析消黄散治疗马火热壅盛证作用机制的研究[J].中国预防兽医学报,2018,40(9):842-846.BAI D D,LI X P,YANG F,et al.The mechanism of Xiaohuangsan powder in treating horses heat syndrome based on network pharmacology[J].Chinese Journal of Preventive Veterinary Medicine,2018,40(9):842-846.(in Chinese with English abstract)
[11] 白东东,李新圃,杨峰,等.基于网络药理学分析白头翁汤治疗猪腹泻的作用机制[J].中国畜牧兽医,2018,45(10):2866-2875.BAI D D,LI X P,YANG F,et al.The mechanism analysis of Baitouweng decoction in treating swine diarrhea based on network pharmacology[J].China Animal Husbandry & Veterinary Medicine,2018,45(10):2866-2875.(in Chinese with English abstract)
[12] 李幸生,李雪,林定忠,等.5’-核苷酸酶测定及其在肝胆疾病中的诊断价值[J].疾病监测与控制杂志,2017,11(11):898-900.LI X S,LI X,LIN D Z,et al.Determination of 5-nucleotidase and its diagnostic value in hepatobiliary diseases[J].Journal of Diseases Monitor & Control,2017,11(11):898-900.(in Chinese)
[13] 葛影影,王根林,张震,等.奶牛乳房炎血清学相关指标的变化[J].黑龙江畜牧兽医,2018(3):39-43.GE Y Y,WANG G L,ZHANG Z,et al.Changes of serological indexes of mastitis in dairy cows[J].Heilongjiang Animal Science and Veterinary Medicine,2018(3):39-43.(in Chinese with English abstract)
[14] 李萌,李楠,佟慧丽,等.王不留行对奶牛乳腺上皮细胞磷酸化雌激素受体的影响[J].中国乳品工业,2012,40(8):9-11.LI M,LI N,TONG H L,et al.Effects of Semen Vaccariae on the phosphorylation estrogen receptor-α of bovine mammary gland epithelial cell[J].China Dairy Industry,2012,40(8):9-11.(in Chinese with English abstract)
[2] 杜琳,王丽芳,冯小慧,等.我国部分地区奶牛乳房炎主要病原菌的分离鉴定及药敏试验[J].动物医学进展,2018,39(3):124-128.DU L,WANG L F,FENG X H,et al.Isolation,identification and drug susceptibility test of main pathogens of dairy cow mastitis in some regions of China[J].Progress in Veterinary Medicine,2018,39(3):124-128.(in Chinese with English abstract)
[3] DEMON D,BREYNE K,SCHIFFER G,et al.Short communication:antimicrobial efficacy of intramammary treatment with a novel biphenomycin compound against Staphylococcus aureus,Streptococcus uberis,and Escherichia coli-induced mouse mastitis[J].Journal of Dairy Science,2013,96(11):7082-7087.
[4] 邢萌茹,刘慧敏,孟璐,等.奶牛乳房炎主要致病菌耐药性研究进展[J].中国乳品工业,2018,46(9):28-35.XING M R,LIU H M,MENG L,et al.Progress on antimicrobial resistance of main pathogens in bovine mastitis[J].China Dairy Industry,2018,46(9):28-35.(in Chinese with English abstract)
[5] 孙静,冶冬阳,王旭荣,等.防治奶牛乳房炎中药组方的筛选及其抑菌杀菌作用研究[J].中国畜牧兽医,2018,45(7):1990-2000.SUN J,YE D Y,WANG X R,et al.Study on screening of traditional Chinese medicine formula and its anti-bacterial effects preventing bovine mastitis[J].China Animal Husbandry & Veterinary Medicine,2018,45(7):1990-2000.(in Chinese with English abstract)
[6] 赛福丁·阿不拉,努尔艾力·麦提尼亚孜,阿依姑丽·买买提明,等.小檗果提取物对奶牛乳房炎常见致病菌体外抑菌和抗炎作用[J].中国兽医学报,2018,38(6):1197-1200.SAIFUDING A,NU ERAILIM M,AYIGULI M,et al.Effect of extract of berberine fruit on antimicrobial and anti-inflammatory effects of common pathogens in cow mutitis[J].Chinese Journal of Veterinary Science,2018,38(6):1197-1200.(in Chinese with English abstract)
[7] 刘艳,罗永江,辛蕊华,等.中药对牛免疫调节作用研究进展[J].动物医学进展,2016,37(6):95-98.LIU Y,LUO Y J,XIN R H,et al.Advance in immunomodulating effects of Chinese medicine on cattle[J].Progress in Veterinary Medicine,2016,37(6):95-98.(in Chinese with English abstract)
[8] 孙雨辉,陆景坤,王健,等.基于网络药理学的三味檀香散治疗冠心病的机制初探[J].中国新药与临床杂志,2018,37(5):272-289.SUN Y H,LU J K,WANG J,et al.A preliminary study on mechanisms of Sanwei Tanxiang powder based on network pharmacology[J].Chinese Journal of New Drugs and Clinical Remedies,2018,37(5):272-289.(in Chinese with English abstract)
[9] 范文涛,王倩.基于网络药理学的石菖蒲-郁金药对治疗抑郁症作用机制研究[J].中国中药杂志,2018,43(12):2607-2611.FAN W T,WANG Q.Mechanism of Acori Tatarinowii Rhizoma-Curcumae Radix treating depression based on network pharmacology[J].China Journal of Chinese Materia Medica,2018,43(12):2607-2611.(in Chinese with English abstract)
[10] 白东东,李新圃,杨峰,等.基于网络药理学分析消黄散治疗马火热壅盛证作用机制的研究[J].中国预防兽医学报,2018,40(9):842-846.BAI D D,LI X P,YANG F,et al.The mechanism of Xiaohuangsan powder in treating horses heat syndrome based on network pharmacology[J].Chinese Journal of Preventive Veterinary Medicine,2018,40(9):842-846.(in Chinese with English abstract)
[11] 白东东,李新圃,杨峰,等.基于网络药理学分析白头翁汤治疗猪腹泻的作用机制[J].中国畜牧兽医,2018,45(10):2866-2875.BAI D D,LI X P,YANG F,et al.The mechanism analysis of Baitouweng decoction in treating swine diarrhea based on network pharmacology[J].China Animal Husbandry & Veterinary Medicine,2018,45(10):2866-2875.(in Chinese with English abstract)
[12] 李幸生,李雪,林定忠,等.5’-核苷酸酶测定及其在肝胆疾病中的诊断价值[J].疾病监测与控制杂志,2017,11(11):898-900.LI X S,LI X,LIN D Z,et al.Determination of 5-nucleotidase and its diagnostic value in hepatobiliary diseases[J].Journal of Diseases Monitor & Control,2017,11(11):898-900.(in Chinese)
[13] 葛影影,王根林,张震,等.奶牛乳房炎血清学相关指标的变化[J].黑龙江畜牧兽医,2018(3):39-43.GE Y Y,WANG G L,ZHANG Z,et al.Changes of serological indexes of mastitis in dairy cows[J].Heilongjiang Animal Science and Veterinary Medicine,2018(3):39-43.(in Chinese with English abstract)
[14] 李萌,李楠,佟慧丽,等.王不留行对奶牛乳腺上皮细胞磷酸化雌激素受体的影响[J].中国乳品工业,2012,40(8):9-11.LI M,LI N,TONG H L,et al.Effects of Semen Vaccariae on the phosphorylation estrogen receptor-α of bovine mammary gland epithelial cell[J].China Dairy Industry,2012,40(8):9-11.(in Chinese with English abstract)
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