

浏览全部资源
扫码关注微信
1.北京中医药大学 东直门医院,北京 100700
2.北京中医药大学 第四临床医学院, 山东 枣庄 277100
3.首都医科大学 附属北京中医医院,北京 100010
Received:25 May 2021,
Published Online:28 October 2021,
Published:20 December 2021
移动端阅览
张迪,晏军,钱莹等.扶正透邪方对耐药铜绿假单胞菌肺部感染大鼠免疫稳态的影响及机制[J].中国实验方剂学杂志,2021,27(24):71-77.
ZHANG Di,YAN Jun,QIAN Ying,et al.Effect and Mechanism of Fuzheng Touxie Prescription on Immune Homeostasis of Drug-resistant Pseudomonas aeruginosa Lung Infection Rats[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(24):71-77.
张迪,晏军,钱莹等.扶正透邪方对耐药铜绿假单胞菌肺部感染大鼠免疫稳态的影响及机制[J].中国实验方剂学杂志,2021,27(24):71-77. DOI: 10.13422/j.cnki.syfjx.20212491.
ZHANG Di,YAN Jun,QIAN Ying,et al.Effect and Mechanism of Fuzheng Touxie Prescription on Immune Homeostasis of Drug-resistant Pseudomonas aeruginosa Lung Infection Rats[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(24):71-77. DOI: 10.13422/j.cnki.syfjx.20212491.
目的
2
探讨扶正透邪方及其不同功效在不同时点对耐药铜绿假单胞菌肺部感染大鼠免疫稳态的影响及其机制。
方法
2
将168只大鼠随机分为空白组(
n
=8),模型组(
n
=40),单纯透邪组(
n
=40),早期扶正组(
n
=40)和延迟扶正组(
n
=40),空白组予蒸馏水灌胃;模型组在感染后予蒸馏水灌胃;单纯透邪组在感染后予清热透邪药物免煎颗粒(3.5 g·kg
-1
)灌胃;早期扶正组在感染后予扶正透邪全方免煎颗粒(10.75 g·kg
-1
)灌胃;延迟扶正组在清热透邪药物免煎颗粒灌胃的基础上于感染后第3天加扶正药物免煎颗粒[(3.5+10.75) g·kg
-1
]灌胃;3个治疗组灌胃每日2次,每次2 mL。除空白组外将每个组根据3 h,1 d,3 d,5 d,7 d时间点分为5个小组(
n
=8)。采用酶联免疫吸附测定法(ELISA)检测各组大鼠肿瘤坏死因子-
α
(TNF-
α
),高迁移率族蛋白B1(HMGB1),白细胞介素-10(IL-10)和肿瘤坏死因子-
α
诱导蛋白8样分子-2(TIPE2)的水平,蛋白免疫印迹法(Western blot)检测HMGB1蛋白表达水平。
结果
2
3 h时,与空白组和模型组比较,单纯透邪组、早期扶正组、延迟扶正组TNF-
α
含量均明显升高(
P
<
0.05)。3 d时,与模型组比较,早期扶正组和延迟扶正组TNF-
α
含量明显降低(
P
<
0.05);与透邪组比较,早期扶正组和延迟扶正组TNF-
α
含量均明显降低(
P
<
0.05)。1 d时,与模型组比较,单纯透邪组、延迟扶正组HMGB1含量均明显升高(
P
<
0.05)。5 d时,与模型组比较,延迟扶正组HMGB1含量明显降低(
P
<
0.05)。7 d时,与空白组比较,模型组HMGB1蛋白表达明显升高(
P
<
0.05);与模型组比较,早期扶正组HMGB1蛋白表达明显降低(
P
<
0.05)。3 d时,与模型组比较,早期扶正组、延迟扶正组IL-10含量均明显升高(
P
<
0.05)。5 d时,与单纯透邪组比较,早期扶正组IL-10含量明显升高(
P
<
0.05);7 d时,与单纯透邪组比较,早期扶正组、延迟扶正组IL-10含量均明显降低(
P
<
0.05)。5 d时,与模型组比较,早期扶正组TIPE2含量明显降低(
P
<
0.05)。7 d时,与模型组比较,单纯透邪组、延迟扶正组TIPE2含量均明显降低(
P
<
0.05)。
结论
2
扶正透邪全方或加用扶正药物在早期可促进炎症反应消除病原菌,晚期抑制炎症反应,避免炎症级联效应和肺组织损伤,说明扶正药物在感染后对维持机体免疫稳态具有重要作用。
Objective
2
To investigate the effect and mechanism of Fuzheng Touxie prescription (FZTX) on the immune homeostasis of drug-resistant
Pseudomonas aeruginosa
lung infection in rats at different time points.
Method
2
A total of 168 rats were divided into a blank group (
n
=8),a model group (
n
=40),a Touxie (TX) group (
n
=40),an early Fuzheng (FZ) group (
n
=40), and a delayed FZ group (
n
=40). The blank group was given distilled water by gavage, the model group was given distilled water by gavage after infection,the TX group was given clear heat and penetrate evil drug free decoction granules(3.5 g·kg
-1
) by gavage after infection, the early FZ group was given Fuzheng Touxie whole formula free decoction granules(10.75 g·kg
-1
) by gavage after infection, the delayed FZ group was given clear heat and penetrate evil drug free decoction granules by gavage after infection, on the third day plus Fuzheng drug free decoction granules[(3.5+10.75) g·kg
-1
] by gavage, the three treatment groups were gavaged twice a day, 2 mL each time .Each drug treatment group was divided into five groups according to five time points (3 h,1 d,3 d,5 d, and 7 d), with eight rats in each group. The levels of tumor necrosis factor-
α
(TNF-
α
),high mobility group protein 1(HMGB1),interleukin-10(IL-10), and tumor necrosis factor -
α
-induced protein-8-like2 (TIPE2) were measured by enzyme-linked immunosorbent assay (ELISA), and HMGB1 protein expression level by Western blot.
Result
2
At 3 h,the TNF-
α
content in the drug treatment groups was higher than that in the blank group and the model group (
P
<
0.05). At 3 d,the TNF-
α
content in the early FZ group and the delayed FZ group was lower than that in the model group (
P
<
0.05) and the TX group (
P
<
0.05). At 1 d,the HMGB1 content in the TX group and the delayed FZ group was higher than that in the model group (
P
<
0.05). At 5 d,the HMGB1 content was lower in the delayed FZ group than in the model group (
P
<
0.05). At 7 d,HMGB1 protein expression in the model group was higher than that in the blank group (
P
<
0.05) and the early FZ group (
P
<
0.05). At 3 d,the IL-10 content was significantly higher in both the early FZ group and the delayed FZ group than that in the model group (
P
<
0.05). At 5 d,the IL-10 content was higher in the early FZ group than that in the TX group (
P
<
0.05). At 7 d,the IL-10 content in the early FZ group and the delayed FZ group was lower than that in the TX group (
P
<
0.05). At 5 d,the TIPE2 content in the early FZ group was lower than that in the model group (
P
<
0.05). At 7 d,the TIPE2 content in the TX group and the delayed FZ group was lower than that in the model group (
P
<
0.05).
Conclusion
2
FZTX or modified prescription can promote the inflammatory response to eliminate pathogenic bacteria in the early stage and suppress the inflammatory response in the late stage to avoid the inflammatory cascade effect and lung tissue damage,indicating that Fuzheng drugs have an important role in maintaining the immune homeostasis of the body after infection.
张祎博 , 孙景勇 , 倪语星 , 等 . 2005—2014年CHINET铜绿假单胞菌耐药性监测 [J]. 中国感染与化疗杂志 , 2016 , 16 ( 2 ): 141 - 145 .
FENG W , SUN F , WANG Q , et al . Epidemiology and resistance characteristics of Pseudomonas aeruginosa isolates from the respiratory department of a hospital in China [J]. J Glob Antimicrob Resist , 2017 , 8 : 142 - 147 .
BASSETTI M , ECHOLS R , MATSUNAGA Y , et al . Efficacy and safety of cefiderocol or best available therapy for the treatment of serious infections caused by carbapenem-resistant Gram-negative bacteria (CREDIBLE-CR): a randomised,open-label,multicentre,pathogen-focused,descriptive,phase 3 trial [J]. Lancet Infect Dis , 2021 , 21 ( 2 ): 226 - 240 .
HU N , WANG C , DAI X , et al . Phillygenin inhibits LPS-induced activation and inflammation of LX2 cells by TLR4/MyD88/NF-kappaB signaling pathway [J]. J Ethnopharmacol , 2020 , 248 : 112361 .
丁军颖 , 丁雪霏 , 卢幼然 , 等 . 芪归银对铜绿假单胞菌致肺炎大鼠免疫调节作用初探 [J]. 河北中医药学报 , 2019 , 34 ( 2 ): 1 - 5 .
AGGARWAL R , JAIN A K , MITTAL P , et al . Association of pro- and anti-inflammatory cytokines in preeclampsia [J]. J Clin Lab Anal , 2019 , 33 ( 4 ): e22834 .
WU X , KONG Q , ZHAN L , et al . TIPE2 ameliorates lipopolysaccharide-induced apoptosis and inflammation in acute lung injury [J]. Inflamm Res , 2019 , 68 ( 11 ): 981 - 992 .
冯娟 , 栗艳 , 孙阳 , 等 . 大黄多糖抑制脂多糖引起的TLR-4/NF -κ B通路活化 [J]. 现代生物医学进展 , 2014 , 14 ( 31 ): 6035 - 6038 .
李文星 , 张毅 , 温勃阳 , 等 . 连翘对内毒素作用下大鼠脾脏淋巴细胞Toll样受体4、核因子- κ B及白细胞介素-6、白细胞介素-10的影响 [J]. 中华实验外科杂志 , 2015 , 32 ( 2 ): 288 - 290 .
高洁 , 刘清泉 , 马群 , 等 . 从伏邪理论看耐药菌感染 [J]. 中医杂志 , 2011 , 52 ( 6 ): 536 - 538 .
刘清泉 , 孙宏源 , 高洁 , 等 . 耐药菌感染中医病机探讨及临床中药疗效观察 [J]. 中国中医药现代远程教育 , 2010 , 8 ( 17 ): 213 - 214 .
孔令博 , 刘清泉 , 王兰 , 等 . 芪归银方对多重耐药铜绿假单胞菌感染大鼠淋巴细胞增殖的影响 [J]. 中医杂志 , 2013 , 54 ( 18 ): 1585 - 1587 .
KONG L B , MA Q , GAO J , et al . Effect of Qiguiyin Decoction on multidrug-resistant Pseudomonas aeruginosa infection in rats [J]. Chin J Integr Med , 2015 , 21 ( 12 ): 916 - 921 .
孔令博 , 郭玉红 , 付跃峰 , 等 . 芪归银方对多重耐药铜绿假单胞菌感染大鼠血清IL-1 β 水平的影响 [J]. 世界中医药 , 2016 , 11 ( 10 ): 1966 - 1969 .
赵伟 , 孙国志 . 不同种实验动物间用药量换算 [J]. 畜牧兽医科技信息 , 2010 ( 5 ): 52 - 53 .
王瑜 , 张定林 , 冯伟 , 等 . 小鼠铜绿假单胞菌气管插管滴注法肺部感染模型的建立及评价 [J]. 第三军医大学学报 , 2019 , 41 ( 10 ): 918 - 922 .
ZHANG H , SUN L , ZHI L , et al . Astilbin alleviates sepsis-induced acute lung injury by inhibiting the expression of macrophage inhibitory factor in rats [J]. Arch Pharm Res , 2017 , 40 ( 10 ): 1176 - 1185 .
HAN Y , KANG C , KANG M , et al . Long non-coding RNA Mirt2 prevents TNF- α -triggered inflammation via the repression of microRNA-101 [J]. Int Immunopharmacol , 2019 , 76 : 105878 .
VIJAYAKUMAR E C , BHATT L K , PRABHAVALKAR K S . High mobility group box-1 (HMGB1):a potential target in therapeutics [J]. Curr Drug Targets , 2019 , 20 ( 14 ): 1474 - 1485 .
XU X , PIAO H N , AOSAI F , et al . Arctigenin protects against depression by inhibiting microglial activation and neuroinflammation via HMGB1/TLR4/NF-kappaB and TNF-alpha/TNFR1/NF-kappaB pathways [J]. Br J Pharmacol , 2020 , 177 ( 22 ): 5224 - 5245 .
RAO Z , ZHANG N , XU N , et al . 1,25-dihydroxyvitamin D inhibits LPS-induced high-mobility group box 1 (HMGB1) secretion via targeting the NF-E2-related factor 2-hemeoxygenase-1-HMGB1 Pathway in macrophages [J]. Front Immunol , 2017 , 8 : 1308 .
YANG H , WANG H , ANDERSSON U . Targeting inflammation driven by HMGB1 [J]. Front Immunol , 2020 , 11 : 484 .
EKANAYAKA S A , MCCLELLAN S A , PENG X , et al . HMGB1 antagonist,box A,reduces TLR4,RAGE,and inflammatory cytokines in the cornea of p.aeruginosa-infected mice [J]. J Ocul Pharmacol Ther , 2018 , 34 ( 10 ): 659 - 669 .
HERMANKOVA B , ZAJICOVA A , JAVORKOVA E , et al . Suppression of IL-10 production by activated B cells via a cell contact-dependent cyclooxygenase-2 pathway upregulated in IFN- γ -treated mesenchymal stem cells [J]. Immunobiology , 2016 , 221 ( 2 ): 129 - 136 .
KULKARNI U , KARSTEN C M , KOHLER T , et al . IL-10 mediates plasmacytosis-associated immunodeficiency by inhibiting complement-mediated neutrophil migration [J]. J Allergy Clin Immunol , 2016 , 137 ( 5 ): 1487 - 1497 .
WANG Q , MA L , LIU T , et al . TIPE2 suppresses Pseudomonas aeruginosa keratitis by inhibiting NF- κ B signaling and the infiltration of inflammatory cells [J]. J Infect Dis , 2019 , 220 ( 6 ): 1008 - 1018 .
NITURE S , DONG X , ARTHUR E , et al . Oncogenic role of tumor necrosis factor α -induced protein 8 (TNFAIP8) [J]. Cells , 2019 , 8 ( 1 ): 9 .
王玉婷 , 徐红日 , 赵世同 , 等 . 扶正解毒化瘀方对多重耐药铜绿假单胞菌MexAB-OprM外排泵表达影响的研究 [J]. 世界中医药 , 2019 , 14 ( 4 ): 859 - 863 .
0
Views
14
下载量
3
CSCD
Publicity Resources
Related Articles
Related Author
Related Institution
京公网安备11010802024621