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Bushen Jianpi Jiedu Liyan Formula Regulates Homing-associated Cell Adhesion Molecules in Rat Model of IgA Nephropathy
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 29, Issue 18, Pages: 36-44(2023)
- 作者机构：
长春中医药大学 附属医院，长春 130021
- 作者简介：
- 基金信息：
DOI：10.13422/j.cnki.syfjx.20232090
CLC： R242;R2-031;R287;R285.5;R692;R256.5Published：20 September 2023，
Published Online：22 March 2022，
Received：21 August 2021，
- 稿件说明：
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张洪宝,张守琳.补肾健脾解毒利咽法对IgA肾病模型大鼠归巢相关黏附分子的影响[J].中国实验方剂学杂志,2023,29(18):36-44.
ZHANG Hongbao,ZHANG Shoulin.Bushen Jianpi Jiedu Liyan Formula Regulates Homing-associated Cell Adhesion Molecules in Rat Model of IgA Nephropathy[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(18):36-44.
张洪宝,张守琳.补肾健脾解毒利咽法对IgA肾病模型大鼠归巢相关黏附分子的影响[J].中国实验方剂学杂志,2023,29(18):36-44. DOI： 10.13422/j.cnki.syfjx.20232090.
ZHANG Hongbao,ZHANG Shoulin.Bushen Jianpi Jiedu Liyan Formula Regulates Homing-associated Cell Adhesion Molecules in Rat Model of IgA Nephropathy[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(18):36-44. DOI： 10.13422/j.cnki.syfjx.20232090.
摘要
目的
2
探讨补肾健脾解毒利咽法不同剂量中药对免疫球蛋白A（IgA）肾病模型大鼠小肠及骨髓中黏附分子整合素
α
4
β
1
与血管细胞黏附分子-1（VCAM-1）、基质细胞衍生因子-1（SDF-1）与趋化因子受体-4（CXCR4）表达的影响。
方法
2
采用雄性SD大鼠120只，应用牛血清白蛋白（BSA）灌胃、CCl
4
皮下注射、脂多糖（LPS）尾静脉注射等方案的改良法制备IgA肾病大鼠模型后，验证模型成功后，随机将大鼠分为空白组、模型组、洛汀新组（63 mg·kg
-1
）、补肾健脾解毒利咽法（中药）低、中、高剂量组（10.4、20.81、41.62 g·kg
-1
），每组16只，给药7周后处死大鼠，收集相关标本并检验，采用免疫组化检测大鼠小肠固有膜黏附分子
α
4
β
1
，VCAM-1，SDF-1和CXCR4的蛋白表达，实时荧光定量聚合酶链式反应（Real-time PCR）检测大鼠骨髓中黏附分子
α
4
β
1
，VCAM-1，SDF-1和CXCR4 mRNA表达变化情况。
结果
2
与空白组比较，第10、12、14、16周模型组大鼠的尿红细胞计数均显著升（
P
<
0.01）。与模型组比较，第10、12、14、16周洛汀新组与中药各剂量组大鼠尿红细胞计数均明显降低（
P
<
0.05），其中中药中剂量组对于大鼠尿红细胞计数改善更明显（
P
<
0.05）。与空白组比较，模型组大鼠小肠固有膜黏附分子
α
4
β
1
，VCAM-1，SDF-1和CXCR4蛋白表达均明显升高（
P
<
0.05）。与模型组比较，洛汀新组及中药各剂量组大鼠小肠固有膜
α
4
β
1
，VCAM-1，SDF-1和CXCR4蛋白表达均明显下降（
P
<
0.05）。与模型组比较，中药中剂量组大鼠小肠固有膜SDF-1与CXCR4蛋白表达均明显下降（
P
<
0.05）。与空白组比较，模型组大鼠骨髓黏附分子
α
4
β
1
，SDF-1 mRNA表达明显下降，VCAM-1，CXCR4 mRNA表达明显升高（
P
<
0.05）。与模型组比较，洛丁新组与中药各剂量组大鼠骨髓黏附分子SDF-1，CXCR4 mRNA均明显下降（
P
<
0.05）。
结论
2
补肾健脾解毒利咽法通过调节小肠固有膜及骨髓中黏附分子
α
4
β
1
与VCAM-1、SDF-1与CXCR4的表达，从而调节浆细胞的归巢效应，可能与Toll样受体介导的免疫应答激活有关，补肾健脾解毒利咽法中药可能通过减少相关黏附分子的表达量从而浆细胞在循环中的增殖，进而减轻IgA肾病肾脏损伤。
Abstract
Objective
2
To investigate the effect of Bushen Jianpi Jiedu Liyan formula on the expression of integrin alpha 4 beta 1 （
α
4
β
1
）， vascular cell adhesion molecule-1 （VCAM-1）， stromal-derived factor-1 （SDF-1）， and chemokine receptor-4 （CXCR4） in the small intestine and bone marrow of the rat model of immunoglobulin A（IgA） nephropathy.
Method
2
A total of 120 male SD rats were used to establish the IgA nephropathy model by intragastric administration of bovine serum albumin （BSA）， subcutaneous injection of CCl
4
， and tail vein injection of lipopolysaccharide （LPS）. The successfully modeled rats were randomized into blank， model， lotensin （63 mg·kg
-1
）， and low-， medium-， and high-dose （10.4， 20.81， 41.62 g·kg
-1
， respectively） Bushen Jianpi Jiedu Liyan formula groups （
n
=16）. The rats were treated with corresponding drugs according to their body weight. After 7 weeks of administration， the rats were sacrificed for the collection of samples， and the protein and mRNA levels of
α
4
β
1
， VCAM-1， SDF-1， and CXCR4 in the small intestine and bone marrow were determined by immunohistochemistry and real-time fluorescence quantitative polymerase chain reaction， respectively.
Result
2
Compared with the blank group， the model group showed increased red blood cell count in the urine at the 10
th
， 12
th
， 14
th
， 16
th
weeks （
P
<
0.01）， and such increases were reduced in the drug intervention groups （
P
<
0.05）， especially in the medium-dose Bushen Jianpi Jiedu Liyan formula group （
P
<
0.05）. Compared with those in the blank group， the protein levels of
α
4
β
1
， VCAM-1， SDF-1， and CXCR4 in the intestinal lamina propria in the model group were up-regulated （
P
<
0.05）， and such un-regulations were inhibited in the drug intervention groups （
P
<
0.05）. Compared with the model group， medium-dose Bushen Jianpi Jiedu Liyan formula down-regulated the protein levels of SDF-1 and CXCR4 in the intestinal lamina propria （
P
<
0.05）. Compared with the blank group， the model group showed down-regulated mRNA levels of
α
4
β
1
and SDF-1 and up-regulated mRNA levels of VCAM-1 and CXCR4 （
P
<
0.05）. Compared with the model group， the drug intervention groups showed down-regulated mRNA levels of SDF-1 and CXCR4 （
P
<
0.05）.
Conclusion
2
Bushen Jianpi Jiedu Liyan formula regulates the expression of
α
4
β
1
， VCAM-1， SDF-1， and CXCR4 in the intestinal lamina propria to inhibit the homing effect of plasma cells， which may be associated with the Toll-like receptor-mediated activation of immune response. Bushen Jianpi Jiedu Liyan formula can down-regulate the expression of adhesion molecules to inhibit the proliferation of plasmocytes in circulation， so as to reduce the renal injury of IgA nephropathy.
关键词
补肾健脾解毒利咽法免疫球蛋白A（IgA）肾病整合素α4 β1血管细胞黏附分子-1（VCAM-1）基质细胞衍生因子-1（SDF-1）趋化因子受体-4（CXCR4）
Keywords
Bushen Jianpi Jiedu Liyan formulaimmunoglobulin A（IgA） nephropathyintegrin alpha 4 beta 1 （α4 β1）vascular cell adhesion molecule-1 （VCAM-1）stromal-derived factor-1 （SDF-1）chemokine receptor-4 （CXCR4）
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