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中国中医科学院 中药研究所 中药鉴定与安全性检测评估北京市重点实验室, 创新天然药物与中药注射剂国家重点实验室,北京 100700
李春英,副主任技师,从事中药药理学与毒理学研究,E-mail:cyli@icmm.ac.cn
* 梁爱华,研究员,博士生导师,从事中药药理学与毒理学研究,E-mail:ahliang@icmm.ac.cn
收稿日期:2021-07-19,
网络出版日期:2021-10-18,
纸质出版日期:2021-12-05
移动端阅览
李春英,易艳,赵雍等.香丹注射液和清开灵注射液联合用药对急性炎症血栓模型大鼠脏器的保护作用[J].中国实验方剂学杂志,2021,27(23):80-87.
LI Chun-ying,YI Yan,ZHAO Yong,et al.Synergistic Effect of Xiangdan Injection and Qingkailing Injection on Organ Injury Caused by Acute Inflammation and Thrombosis in Rats[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(23):80-87.
李春英,易艳,赵雍等.香丹注射液和清开灵注射液联合用药对急性炎症血栓模型大鼠脏器的保护作用[J].中国实验方剂学杂志,2021,27(23):80-87. DOI: 10.13422/j.cnki.syfjx.20212302.
LI Chun-ying,YI Yan,ZHAO Yong,et al.Synergistic Effect of Xiangdan Injection and Qingkailing Injection on Organ Injury Caused by Acute Inflammation and Thrombosis in Rats[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(23):80-87. DOI: 10.13422/j.cnki.syfjx.20212302.
目的
2
基于血栓变化、炎性指标、脏器功能和病理改变等考察香丹注射液(Xiangdan injection,XDI)和清开灵注射液(Qingkailing injection, QKLI)联合用药在炎症血栓动物模型的治疗上是否具有协同增效作用。
方法
2
100只雄性SD大鼠,根据体质量随机分为正常组,炎症血栓模型组,XDI组(2.5,5 mL·kg
-1
),QKLI组(5,10 mL·kg
-1
),XDI+QKLI组[(2.5+5) mL·kg
-1
,(2.5+10) mL·kg
-1
,(5+5) mL·kg
-1
,(5+10) mL·kg
-1
,每组10只大鼠。各组均腹腔注射给与相应注射液,每天1次,共4 d,正常组和模型组注射生理盐水。给药第2天,除正常组外,其余各组大鼠均造模,即先采用25 mg·kg
-1
角叉菜胶腹腔注射入大鼠体内,16 h后大鼠再尾静脉注射50 μg·kg
-1
脂多糖(LPS)。注射LPS 24 h后,各组大鼠测定肝脏指数、肾脏指数,测定血小板(PLT)数量,测量血栓长度,全自动生化分析仪测定各项肝肾功能天门冬氨酸氨基转移酶(AST),丙氨酸氨基转移酶(ALT),碱性磷酸酶(ALP),肌酐(Crea)及尿素氮(BUN),酶联免疫吸附测定法(ELISA)检测炎性因子白细胞介素-6(IL-6)和肿瘤坏死因子-
α
(TNF-
α
)含量,苏木素-伊红(HE)染色观察心、肝、肺、肾脏组织病理学变化,以及观察脏器病变分级情况。
结果
2
与正常组比较,模型组大鼠PLT数量显著下降,大鼠尾部血栓长度显著增加,肝脏指数显著升高,肝肾功能ALT,ALP,BUN含量明显升高,IL-6和TNF-
α
含量明显升高(
P
<
0.05,
P
<
0.01),肝、肺、肾脏组织出现明显病理损伤(
P
<
0.05,
P
<
0.01)。与模型组比较,XDI 5 mL·kg
-1
组明显降低大鼠血清ALT和ALP含量(
P
<
0.05,
P
<
0.01),QKLI 5,10 mL·kg
-1
组大鼠血清ALT,ALP和TNF-
α
含量明显下降(
P
<
0.05,
P
<
0.01),XDI 5 mL·kg
-1
和QKLI 10 mL·kg
-1
单独用药均对LPS引起的肺脏病变损伤有明显减轻作用(
P
<
0.05);XDI和QKLI合用后,明显降低大鼠的ALT,AST,ALP和TNF-
α
含量,尤其是XDI和QKLI合用(5+10) mL·kg
-1
组效果最为明显(
P
<
0.05,
P
<
0.01),并且大鼠尾部血栓长度明显缩短(
P
<
0.05),肺脏病变程度也减轻(
P
<
0.05)。与部分相同剂量XDI或QKLI单用组比较,两药合用后,大鼠血清ALT,BUN,TNF-
α
含量和肝脏指数都明显下降(
P
<
0.05,
P
<
0.01)。
结论
2
XDI和QKLI单独用药对炎症血栓模型大鼠的脏器功能和器质损害及炎症反应有一定改善作用和抑制作用。两者合用后相对其单独用药,对于减少静脉血栓长度,改善肝肾功能,降低炎性因子,保护肺、肝、肾等脏器结构都有一定协同增效作用。
Objective
2
To investigate the synergistic effect of Xiangdan injection (XDI) and Qingkailing injection (QKLI) in the treatment of inflammation and thrombosis animal model based on changes of thrombus, inflammatory indexes, organ function, and pathological changes.
Method
2
A total of 100 male SD rats were randomly divided into a normal control group, a model group, XDI groups (2.5, 5 mL·kg
-1
), QKLI groups (5, 10 mL·kg
-1
), and XDI + QKLI groups [(2.5+5) mL·kg
-1
,(2.5+10) mL·kg
-1
,(5+5) mL·kg
-1
,and (5+10) mL·kg
-1
] according to the body weight, with 10 rats in each group. Rats were treated correspondingly by intraperitoneal injection once a day for 4 days. The normal control group and the model group received normal saline. On the second day of administration, the model was induced in rats except those in the normal control group. Specifically, 25 mg·kg
-1
carrageenan was injected intraperitoneally into the rats, followed by an injection of 50 μg·kg
-1
lipopolysaccharide (LPS) through the tail vein 16 hours later. Twenty-four hours after LPS injection, the rats were detected for liver index, kidney index, the number of platelets (PLT), thrombus length, and biochemical indicators such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatinine, and blood urea nitrogen (BUN). Enzyme-linked immunosorbent assay (ELISA) was used to determine the content of inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-
α
(TNF-
α
). Hematoxylin-eosin (HE) staining was used to observe the histopathological changes of heart, liver, lung, and kidney, as well as the grading of organ injury.
Result
2
Compared with the normal group, the model group showed decreased PLT, lengthened thrombus in the tail, increased liver index, elevated content of ALT, ALP, BUN, IL-6, and TNF-
α
(
P
<
0.05,
P
<
0.01), and damaged liver, lung, and kidney tissues (
P
<
0.05,
P
<
0.01). Compared with the conditions in the model group, XDI at 5 mL·kg
-1
reduced serum ALT and ALP in rats (
P
<
0.05,
P
<
0.01), QKLI at 5 and 10 mL·kg
-1
reduced serum levels ALT and ALP, and TNF-
α
content
(
P
<
0.05,
P
<
0.01). XDI at 5 mL·kg
-1
or QKLI at 10 mL·kg
-1
relieved the LPS-induced lung injury (
P
<
0.05), the combination of XDI and QKLI decreased the levels of ALT, AST, ALP, and TNF-
α,
and the effect was predominant in the combination of XDI and QKLI at 5 and 10 mL·kg
-1
(
P
<
0.05,
P
<
0.01). Additionally, the length of the tail thrombus was significantly shortened (
P
<
0.05), and the degree of lung injury was also reduced (
P
<
0.05). The serum levels of ALT and BUN, TNF-
α
content, and liver index of rats were reduced after the combination of XDI and QKLI as compared with those in the single drug groups at the same dose (
P
<
0.05,
P
<
0.01).
Conclusion
2
XDI or QKLI can improve or inhibit organ function, organ injury, and inflammatory response in the rat model of inflammation and thrombosis. The combination of the two drugs shows a synergistic effect in reducing the length of venous thrombus, improving liver and kidney function, inhibiting inflammatory factors, and protecting lung, liver, kidney, and other organs.
MAJUMDAR S , CHATTOPADHYAY P , MUKHERJEE A K . In vivo anticoagulant and thrombolytic activities of a fibrinolytic serine protease (brevithrombolase) with the k-carrageenan-induced rat tail thrombosis model [J]. Clin Appl Thromb Hemost , 2016 , 22 ( 6 ): 594 - 599 .
梁爱华 , 刘婷 , 李春英 , 等 . 一种热毒诱导的血栓形成动物模型的建立 [J]. 中国中药杂志 , 2008 , 33 ( 18 ): 2124 - 2128 .
BUDNIK I , BRILL A . Immune factors in deep vein thrombosis initiation [J]. Trends Immunol , 2018 , 39 ( 8 ): 610 - 623 .
ONG S B , S HERNÁNDEZ-RESÉNDIZ , CRESPO-AVILAN G E , et al . Inflammation following acute myocardial infarction:multiple players,dynamic roles,and novel therapeutic opportunities [J]. Pharmacol Ther , 2018 , 186 : 73 - 87 .
YANG T , CHANG P , LU S . L5-LDL from ST-elevation myocardial infarction patients induces IL-1 beta production via LOX-1 and NLRP3 inflammasome activation in macrophages [J]. Am J Physiol Heart Circ Physiol , 2017 , 312 ( 2 ): 265 - 274 .
余琳 , 武晓灵 . 香丹注射液联合乌司他丁治疗重症急性胰腺炎的疗效及对血液流变学和血清SOD、CRP、IL-6水平的影响 [J]. 中国中西医结合消化杂志 , 2021 , 29 ( 6 ): 421 - 425 .
黄国淳 , 孙艳娜 , 陆桂宁 . 雷公藤多苷联合清热止血方和香丹注射液治疗小儿紫癜性肾炎疗效观察 [J]. 现代中西医结合杂志 , 2018 , 27 ( 5 ): 527 - 529,546 .
马维娜 , 孟拥军 . 清开灵的作用机制及临床应用进展 [J]. 医学综述 , 2016 , 22 ( 23 ): 4664 .
曹春雨 , 梁爱华 , 赵雍 , 等 . 清开灵注射液的抗血栓作用及其机制研究 [J]. 中国中药杂志 , 2009 , 34 ( 12 ): 1549 - 1552 .
YE S , MAO B , YANG L , et al . Thrombosis recanalization by paeoniflorin through the upregulation of urokinase-type plasminogen activator via the MAPK signaling pathway [J]. Mol Med Rep , 2016 , 13 ( 6 ): 4853 - 4858 .
BORGEL D , BIANCHINI E , LASNE D , et al . Inflammation in deep vein thrombosis:a therapeutic target [J]. Hematology , 2019 , 24 ( 1 ): 742 - 750 .
王梦梦 , 吉兰芳 , 崔树娜 . 丹参功效的物质基础研究进展 [J]. 中医学报 , 2019 , 34 ( 5 ): 944 - 949 .
栗意 , 陈敏 , 徐超 , 等 . 丹参素对缺血/再灌注损伤器官保护作用机制研究进展 [J]. 海峡药学 , 2020 , 32 ( 10 ): 1 - 5 .
李跃文 , 刘志强 , 赵越 , 等 . 香丹注射液治疗冠心病主要活性成分-靶点-通路的网络分析 [J]. 中国药学杂志 , 2018 , 53 ( 22 ): 1927 - 1935 .
郭文胜 . 清开灵注射液抗感染基础及临床研究进展 [J]. 临床合理用药杂志 , 2015 , 8 ( 3 ): 168 - 171 .
马丹 , 包先丽 , 叶霜 , 等 . 复方丹参注射液对重症急性胰腺炎肺损伤大鼠CYLD/NF- κ B信号的影响 [J]. 中国中医急症 , 2018 , 27 ( 12 ): 2019 - 2102 .
卢志刚 , 刘芸 , 易继龙 . 清开灵注射液对自发性蛛网膜下腔出血后脑血管痉挛患者SOCS-3,TNF- α 和IL-6的影响[J . 中国医院药学杂志 , 2015 , 35 ( 2 ): 141 - 144 .
CIMMINO G , CIRILLO P . Tissue factor:newer concepts in thrombosis and its role beyond thrombosis and hemostasis [J]. Cardiovasc Diagn Ther , 2018 , 8 ( 5 ): 581 - 593 .
STOJKOVIC S , KAUN C , BASILIO J , et al . Tissue factor is induced by interleukin-33 in human endothelial cells:a new link between coagulation and inflammation [J]. Sci Rep , 2016 , 6 : 1 - 4 .
SUN Y , WANG J , YU L , et al . The role of peroxisome proliferator-activated receptor- γ /nuclear factor- κ B transduction pathway on coagulation disorders induced by sepsis [J]. Chin Crit Care Med , 2015 , 27 ( 6 ): 520 - 524 .
YANG J , ZHOU X , FAN X , et al . mTORC1 promotes aging-related venous thrombosis in mice via elevation of platelet volume and activation [J]. Blood , 2016 , 128 ( 5 ): 615 - 624 .
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