浏览全部资源
扫码关注微信
1.广州中医药大学 中药学院,广州 510006;
2.广州中医药大学 第一临床医学院,广州 510006;
3.佛山市中医院,广东 佛山 528000;
4.广州中医药大学 临床药理研究所,广州 510405
张嘉骏,在读硕士,从事调理脾胃方药的临床和实验研究,E-mail:zjjhero@qq.com
*施旭光,教授,从事调理脾胃方药的临床和实验研究,E-mail:sxg6902@126.com
纸质出版日期:2019-02-20,
网络出版日期:2018-11-06,
收稿日期:2018-07-16,
扫 描 看 全 文
张嘉骏, 施家希, 黄娟, 等. 参苓白术散对溃疡性结肠炎小鼠NLPR3,NLPR6蛋白及相关炎症因子表达的影响[J]. 中国实验方剂学杂志, 2019,25(4):36-41.
Jia-jun ZHANG, Jia-xi SHI, Juan HUANG, et al. Effect of Shenling Baizhu San on Expressions of NLPR3, NLPR6 Protein and Related Inflammatory Factors in Mice with Ulcerative Colitis[J]. Chinese Journal of Experimental Traditional Medical Formulae, 2019,25(4):36-41.
张嘉骏, 施家希, 黄娟, 等. 参苓白术散对溃疡性结肠炎小鼠NLPR3,NLPR6蛋白及相关炎症因子表达的影响[J]. 中国实验方剂学杂志, 2019,25(4):36-41. DOI: 10.13422/j.cnki.syfjx.20190401.
Jia-jun ZHANG, Jia-xi SHI, Juan HUANG, et al. Effect of Shenling Baizhu San on Expressions of NLPR3, NLPR6 Protein and Related Inflammatory Factors in Mice with Ulcerative Colitis[J]. Chinese Journal of Experimental Traditional Medical Formulae, 2019,25(4):36-41. DOI: 10.13422/j.cnki.syfjx.20190401.
目的:
2
探讨参苓白术散对3%葡聚糖硫酸钠(DSS)诱导的溃疡性结肠炎(UC)小鼠的治疗作用及相关的作用机制。
方法:
2
60只雄性SPF级C57BL/6小鼠随机分为正常组,模型组,柳氮磺吡啶组(0.52 g·kg
-1
),参苓白术散高、中、低(31.2,15.6,7.8 g·kg
-1
)剂量组。除正常组外小鼠饮用3%葡聚糖硫酸钠蒸馏水1周造成UC模型。造模结束后每日给药1次,正常组和模型组按20 mL·kg
-1
给予0.9%生理盐水,共14 d。每日观察小鼠体质量、粪便性状及隐血情况并计成疾病活动指数(DAI)评分。给药结束后取血收集血清,取小鼠结肠称质量测量长度并制作病理切片。酶联免疫吸附测定(ELISA)检测血清白细胞介素-18(IL-18),IL-1
β
含量;苏木素-伊红(HE)及阿利新蓝-过碘酸雪夫氏(AB/PAS)染色观察结肠病理情况;蛋白免疫印迹法(Western blot)检测结肠核苷酸结合寡聚化结构域样受体3(NLPR3),NLPR6蛋白表达水平。
结果:
2
与正常组比较,模型组小鼠DAI评分显著升高(
P
<
0.01),结肠质量增加、长度变短(
P
<
0.01);结肠黏膜病理受损严重;血清中IL-1
β
含量明显增高(
P
<
0.05);NLRP3蛋白表达升高,NLRP6表达降低(
P
<
0.01)。给药后,与模型组比较,SASP组与高剂量组DAI评分降低(
P
<
0.05),结肠质量、长度、病理情况均改善;血清中IL-1
β
含量降低(
P
<
0.05);NLRP3蛋白表达降低(
P
<
0.01),NLRP6蛋白表达上调(
P
<
0.05,
P
<
0.01)。
结论:
2
参苓白术散有治疗DSS诱导UC小鼠的作用,其作用机制可能与其调节NLRP3,NLRP6蛋白及相关炎症因子,从而减轻肠道炎症反应,缓解肠黏膜损伤有关。
Objective:
2
To investigate the therapeutic effect and related mechanism of Shenling Baizhu San on 3%dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice.
Method:
2
Sixty male SPF C57BL/6 mice were randomly divided into control group
salazosulfapyridine (SASP
0.52 g·kg
-1
)
and low
medium and high-dose (31.2
15.6
7.8 g·kg
-1
) Shenling Baizhu San groups. Except for the control group
mice in the other groups were given distilled water containing 3%dextran sulfate sodium salt for a week to establish UC models. The drug was administered once a day for 14 days. The normal group and the model group were administered with 0.9%physiological saline at 20 mL·kg
-1
. The mice's body weight
fecal traits
and occult blood were observed daily
and the disease activity index (DAI) was scored. After the end of the administration
the blood was collected
mice colons were collected
weighed and measured for length
and pathological sections were prepared. Enzyme-linked immunosorbent assay (ELISA) kit was used to detect the serum levels of interleukin-18 (IL-18) and IL-1
β
in mice; htoxylin eosin (HE) and alixin blue/schiff periodic acid shiff(AB/PAS) staining were used to observe the pathological changes of colon tissues; Western blot was used to detect the colon tissue of mice nucleotide binding oligomerization domain-like receptor 3 (NLPR3)
NLPR6 protein expression levels.
Result:
2
Compared with the normal group
the DAI score of the model group was increased (
P
<
0.01)
the colon weight was increased
and the length was shortened (
P
<
0.01); the pathological damage of the colonic mucosa was severe; the serum IL-1
β
content increased (
P
<
0.05); NLRP3 protein expression increased
while NLRP6 expression decreased (
P
<
0.01). Compared with the model group
the DAI scores of the SASP group and the high-dose group were decreased (
P
<
0.05)
the colon weight
length
and pathological conditions were improved; the serum IL-1
β
concentration was decreased (
P
<
0.05); NLRP3 protein expression decreased (
P
<
0.01)
and NLRP6 expression was up-regulated (
P
<
0.05
P
<
0.01).
Conclusion:
2
Shenling Baizhu San has the effect in treating DSS-induced UC mice
which may be related to the regulation of NLRP3
NLRP6 protein and related inflammatory factors
so as to reduce intestinal inflammation and alleviate intestinal mucosal damage.
溃疡性结肠炎参苓白术散炎症结肠核苷酸结合寡聚化结构域样受体3(NLPR3)NLPR6白细胞介素-18(IL-18)IL-1β
ulcerative colitisShenling Baizhu Saninflammationnucleotide binding oligomerization domain-like receptor 3 (NLPR3)NLPR6interleukin-18 (IL-18)IL-1β
梁洁,周林,沙素梅,等.炎症性肠病诊断与治疗的共识意见(2012年·广州)溃疡性结肠炎诊断部分解读[J].胃肠病学,2012,17(12):712-720.
Ungaro R,Mehandru S,Allen P B,et al. Ulcerative colitis[J].Lancet, 2017, 389(10080): 1756-1770.
Antoni L,Nuding S,Wehkamp J,et al. Intestinal barrier in inflammatory bowel disease[J].World J Gastroenterol, 2014, 20(5): 1165-1179.
齐雪阳,张勤生,张春燕.芍药汤加减保留灌肠联合美沙拉嗪肠溶片治疗大肠湿热证溃疡性结肠炎[J].中国实验方剂学杂志,2016,22(19):149-153.
Eran E,Till S,Andrew L K,et al.NLRP6 inflammasome is a regulator of colonic microbial ecology and risk for colitis[J].Cell,2011,145(5):745-757.
Wlodarska M,Thaiss C A,Nowarski R,et al. NLRP6 inflammasome orchestrates the colonic host-microbial interface by regulating goblet cell mucus secretion[J].Cell, 2014, 156(5): 1045-1059.
Dupaul-Chicoine J, Yeretssian G, Doiron K, et al. Control of intestinal homeostasis, colitis, and colitis-associated colorectal cancer by the inflammatory caspases[J].Immunity, 2010,32(3):367-378.
Zaki M H, Boyd K L, Vogel P, et al. The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis[J].Immunity,2010,32(3):379-391.
文艺,翁湘涛,胡月,等.参苓白术散方联合西药治疗溃疡性结肠炎的系统评价和Meta分析[J].广州中医药大学学报,2017,34(2):274-281.
董开忠,高永盛,秦宁恩加,等.参苓白术散对抗生素引起肠道菌群失调小鼠的影响[J].中国实验方剂学杂志,2015,21(1):154-157.
刘玉晖,胡婕,易文凤,等.参苓白术散治疗炎症性肠病与肠上皮细胞紧密连接的关系探讨[J].中国实验方剂学杂志,2015,21(3):130-133.
刘蕾蕾,施丽婕.葡聚糖硫酸钠致溃疡性结肠炎动物模型研究进展[J].长春中医药大学学报,2015,31(1):207-209.
Lombardi Valter R M,Etcheverría I,Carrera I, et al. Prevention of chronic experimental colitis induced by dextran sulphate sodium (DSS) in mice treated with FR91[J].J Biomed Biotechnol, 2010,114(3):385-391.
HE J,LIANG J,ZHU S,et al. Protective effect of taurohyodeoxycholic acid from Pulvis Fellis Suis on trinitrobenzene sulfonic acid induced ulcerative colitis in mice[J].Eur J Pharmacol, 2011, 670(1): 229-235.
桑婷婷,郭铖洁,郭丹丹,等.中医药通过调节肠道菌群抑制肥胖和炎症相关疾病的进展研究[J].中国中药杂志,2018,43(16):3235-3242.
SHEN H H,YANG Y X, MENG X,et al. NLRP3: a promising therapeutic target for autoimmune diseases[J].Autoimmun Rev,2018,17(7):694-702.
Perera A P,Kunde D,Eri R. NLRP3 inhibitors as potential therapeutic agents for treatment of inflammatory bowel disease[J].Curr Pharm Des, 2017, 23(16): 2321-2327.
丁凌辉,贾育新,成映霞,等.参苓白术散对脾虚湿困型溃疡性结肠炎大鼠结肠IL-13,IL-23及COX-2,CREB表达的影响[J].中国实验方剂学杂志,2018,24(11):67-72.
0
浏览量
9
下载量
7
CSCD
关联资源
相关文章
相关作者
相关机构