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| MAPK p38 pathway may be involved in renal function improvement in chronic renal failure rats treated with Jianpi Qinghua Decoction |
| MA Xiao-Hong1,2, ZOU Bin,1 ZHANG Yue3, HE Li-Qun1,2 |
| 1.Department of Nephropathy，Shuguang Hospital，Shanghai University of Traditional Chinese Medicine，Shanghai 201203，China；2.Clinical Key Laboratory of Traditional Chinese Medicine，Shanghai 201203,China；3.Chinese Medicine Research Center，Shanghai University of Traditional Chinese Medicine，Shanghai 200021,China |
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Abstract Objective： To investigate the involvement of MAPK p38 pathway in treatment of chronic renal failure with Jianpi Qinghua Decoction in rats.
Methods： Forty SPF SD rats were divided into sham group（n=10），model group（n=10），Jianpi Qinghua group（n=10） and losartan group（n=10）. Rat chronic renal failure was induced by 5/6 nephrectomy (Platt method) in model，Jianpi Qinghua and losartan groups，and rats in sham group received sham operation. Jianpi Qinghua decoction (3.9 g·200 g-1) or losartan (3.3 g·200 g-1) daily were administrated by gavage in Jianpi Qinghua and losartan groups for 60 days，respectively. Rats in sham and model groups were orally administered with saline of the same volume. The serum levels of creatinine and urea nitrogen were measured by biochemical method，the expression of MAPK p38 was detected by Western Blot，and renal pathological changes were observed with hematoxylin-eosin staining.
Results： Compared to model group，serum creatinine levels after 60d in Jianpi Qinghua and losartan groups were decreased significantly (42.67±5.98 or 40.90±5.07 vs 60.90±9.54，both P<0.01), the expression of MAPK p38 was significantly down-regulated (0.555±0.004 or 0.587±0.045 vs 0.930±0.265，both P<0.01) and serum urea nitrogen was also decreased (8.56±0.75 or 7.97±0.86 vs 8.62±0.62，both P<0.05). The renal pathology in the model group presented glomerular mesangial proliferation，hyperplasia of glomenrulus mesangial cells and interstitial inflammation. Those pathological changes were attenuated significantly in Jianpi Qinghua and losartan groups.
Conclusion： Jianpi Qinghua Decoctions can improve the renal function and renal pathological changes in a rat with chronic renal failure，which may be associated with down-regulation of MAPK p38 immune inflammatory pathways.
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Received: 30 October 2012
Published: 25 September 2013
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丝裂原活化的蛋白激酶p38在健脾清化方改善大鼠慢性肾衰竭中的意义
目的：探讨丝裂原活化蛋白激酶（MAPK）p38在健脾清化方改善模型大鼠慢性肾衰竭肾纤维化中的作用。
方法：SPF级SD大鼠分为假手术组（n=10）、模型组（n=10）、健脾清化方组（n=10）、氯沙坦组（n=10）。健脾清化方组每日灌胃1次，每次3.9 g/200 g大鼠，连续60 d；氯沙坦组每日灌胃1次，每次3.3 g/200 g大鼠，连续60 d；假手术组和模型组等体积生理盐水灌胃。5/6肾切除大鼠模型（Platt法），采用生化法检测大鼠血清肌酐、尿素氮，蛋白质印迹法检测MAPK p38，HE染色观察肾脏组织病理学变化。
结果：与模型组比较，健脾清化方、氯沙坦能显著降低血清肌酐水平(42.67±5.98 vs 60.90±9.54，40.90±5.07 vs 60.90±9.54，均P<0.01)及MAPK p38表达(0.555±0.004 vs 0.930±0.265，0.587±0.045 vs 0.930±0.265，均P<0.01)，降低大鼠血清尿素氮水平(8.56±0.75 vs 8.62±0.62，7.97±0.86 vs 8.62±0.62，均P<0.05)；模型组可见肾小球增生，系膜细胞轻度增生，间质炎性细胞浸润，健脾清化方组、氯沙坦组与模型组比较病变明显减轻，且健脾清化方组较氯沙坦组病变减轻更明显。
结论：健脾清化方对Platt模型大鼠的肾功能和肾脏病理有一定的改善作用，该机制可能与健脾清化方对MAPK p38相关免疫炎症通路的抑制有关。
关键词：
中草药/治疗应用,
p38丝裂原活化蛋白激酶类,
肾功能衰竭,慢性/病理学,
肾功能衰竭,
纤维化,
血尿素氮,
疾病模型,动物
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[1]NANGAKU M.Mechanisms of tubulointerstitial injury in the kidney:final common pathways to end-stage renal failure
[J].Intern Med，2004，43(1):9-17.
[2]HE Liqun，CAI Gan(何立群，蔡淦).Clinical study of chronic renal failure with syndrome of dampness2heat due to spleen deficiency treated with Jianpi Qinghua Recipe
[J].Journal of Chinese Integrative Medicine(中西医结合学报)，2005，3(4):270-273.(in Chinese)
[3]HE Liqun，HOU Weiguo，SHEN Peicheng，et al(何立群，侯卫国，沈沛成，等).Clinical Observation of “Jianpi Qinghua Decoction” in Treating Chronic Renal Failure of Spleen- Deficiency and Dampness- Heat and Its Effect on cell Molecular Biology
[J].Shanghai Journal of Traditional Chinese Medicine(上海中医药杂志)，2006，40(4):6-8.(in Chinese)
[4]CHEN Gang，HE Liqun(陈刚，何立群).Clinical Observation of 53 CRF patients treated with Jianpi Qinghua Decoction
[J].Chinese Journal of Integrated Traditional and Western Nephrology(中国中西医结合肾病杂志)，2006，7(10):591-593.(in Chinese)
[5]WU Feng，SUN Yue，ZHANG Tong，et al(吴锋，孙悦，张彤，等).A multicenter，randomized，open-label study of “Jian Pi Qing Hua Decoction”on Microinflammatory State in CKD2～3
[J].Chinese Journal of Integrated Traditional and Western Nephrology(中国中西医结合肾病杂志)，2012，13(6):504-506.(in Chinese)
[6]JI R R，GEREAU RW 4th MALCANGIO M，et al．MAP kinase and pain
[J].Brain Res Rev，2009，60(1):135-148．
[7]NICK J A，YOUNG S K，AMDT P G，et al.Selective supp ression of neutro2 phil accumulation in ongoing pulmonary inflammation by systemic inhibition of p38 mitogen2activated p rotein kinase
[J].J Immunol，2002，169(9):5260-5269.
[8]SHEN Xiawei，DENG Deming，SUN Aiping(沈霞蔚，邓德明，孙爱萍).The research progress of p38MAPK in diabetic nephropathy
[J].Journal of Yangtze University(Natural Science Edition ）(长江大学学报:自然科学版)，2011，8(1):206-209.(in Chinese)
[9]CHOW F，OZOlS E，NIKOLIC-PATERSON D J，et al.Macrophages in mouse type 2 diabetic nephropathy:correlation with diabetic state and progressive renal injury
[J].Kidney Int，2004，65(1):116-128.
[10]UNDERWOOD D C，OSBOM R R，BOCHNOWICZ S，et al.SB 239063，a p38 MAPK inhibitor，reduces neut rophilia，inflammatory cytokines，MMP-9，and fibrosis in lung
[J].Am J Physiol Lung Cell Mol Physiol，2000，279(5):L895-902.
[11]MATSUOKA H，ARAI T，MORI M，et al.A p38 MAPK inhibitor，FR-167653，ameliorates murine bleomycininduced pulmonary fibrosis.Am J Physiol Lung Cell Mol Physiol，2002，283(1):L103-112.
[12]LI Qingquan，XU Zude(李清泉，许祖德).Regulatory Mechanism on expression and activity of matrix metalloproteinase
[J].Chinese Journal of Composite Clinical Medicine(中华综合临床医学杂志)，2005，7(6):118.(in Chinese)
[13]CHIN B Y，MOHSENIN A，LI S X，et al.Stimulation of pro-αl( iv) collagen by TGF-β1 in mesangial cells:role of the p38 MAPK pathway
[J].Am J Physiol Renal Physiol，2001，280（3）:F495 - F504.
[14]STAMBE C，ATKINS R C，TESCH G H，et al.The Role of p38 alpha Mitogen-Activated Protein Kinase activation in renal fibrosis
[J].J Am Soc Nephrol，2004，15(2):370-379.
[15]Van den BLINK B，JUFFERMANS N P，TEN Hove T，et al.p38 mitogen-activated protein kinase inhibition increases cytokine release by macrophages in vitro and during infection in vivo
[J].J Immunology，2001，166(1):582-587.
[16]YUAN Cangqing，XING Liang(袁常青，邢亮).Study on processing of Rhubarb and its pharmacological analysis
[J].Chinese Journal of Modern Drug Application(中国现代药物应用)，2010，4(9):122.(in Chinese)
[17]LIU W H,TANG F T,DENG Y H,et al.Berberine reduces fibronectin and collagen accumulation in rat glomerularmesangial cells cultured under high glucose condition
[J].Molecular and Cellular Bio-chemistry，2009，325(1-2):99.
[18]FU Qiang，HE Liqun，CAO Hexin(符强，何立群，曹和欣).Effects of Jianpi Qinghua Recipe on oxygen radicals and transforming growth factorβ1 in renal tissue in a rat model of chronic renal failure with hyperlipidemia
[J].Journal of Chinese Integrative Medicine(中西医结合学报)，2006，4(4):408- 412.(in Chinese)
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