[an error occurred while processing this directive]

Journal of Chinese Integrative Medicine ›› 2008, Vol. 6 ›› Issue (8): 810-816.doi: 10.3736/jcim20080808

• Original Experimental Research • Previous Articles     Next Articles

Effects of rhubarb aglycone on matrix metalloproteinase in cerebral ischemic tissue in rats with bone marrow mesenchymal stem cell transplantation

Jian-sheng Li1(), Jing-xia Liu1, Jie Sun1, Yue-wu Zhao2, Jing Su1, Ning Li1, Xiao-yan Guo1   

  1. 1. Institute of Geriatrics, Henan College of Traditional Chinese Medicine, Zhengzhou, Henan Province 450008, China
    2. Department of Pathology, Henan Province People's Hospital, Zhengzhou, Henan Province 450003, China
  • Received:2007-11-22 Online:2008-08-20 Published:2008-08-15

RichHTML

2

PDF (PC)

67

Like

Objective: To observe the effects of rhubarb aglycone on pathological changes and activity of matrix metalloproteinase in cerebral ischemic tissue in rats with bone marrow mesenchymal stem cell (BMSC) transplantation, and to explore the action mechanisms of rhubarb aglycone in protecting against brain micrangium injury in rats.
Methods: The BMSCs were purified and amplified by methods of adherence and selection in vitro. One hundred and ninety rats were randomly divided into sham-operated group, untreated group, rhubarb aglycone group, BMSC transplantation group (abbreviated as transplantation group) and BMSCs combined with rhubarb aglycone group (abbreviated as combination group). Middle cerebral artery occlusion (MCAO) model was duplicated with nylon thread. Rats of transplantation and combination group were transplanted with BMSCs via carotid artery after 24-hour reperfusion. Rhubarb aglycone was used by intragastric administration in the rhubarb aglycone group and the combination group. The brain samples were taken at 7, 14 and 28 days after transplantation. Brain micrangium pathological changes were observed by light microscope, and immunohistochemical method was used to determine the expressions of immunoglobulin G (IgG), type Ⅳ collagen (col Ⅳ), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1).
Results: Comparison with the normal control group revealed that brain micrangium in rats in the untreated group was obviously mutilated and damaged, the expression of IgG and MMP-9 increased, and showed a progressively enhanced tendency following the prolongation of reperfusion, while the expressions of col Ⅳ and TIMP-1 were decreased, and TIMP-1 showed a attenuated tendency following the prolongation of reperfusion. Comparing with the untreated group, the improvements of brain micrangium structure in the rhubarb aglycone group (7 days after transplantation), the transplantation group (14 and 28 days after transplantation) and the combination group were significant; expression of IgG and activity of MMP-9 were decreased, while expressions of Col Ⅳ and TIMP-1 were increased in the rhubarb aglycone group and the combination group at each time point. The brain micrangium was integral and the expression of Col Ⅳ was enhanced in combination group (7 days after transplantation) as compared with those in transplantation group. MMP-9 activity in combination group (14 days after transplantation) was lower than that in the rhubarb aglycone group (14 days after transplantation), while expression of TIMP-1 in combination group also increased significantly as compared with that in transplantation group (28 days after transplantation).
Conclusion: Rhubarb aglycone can decrease the degradation of basal lamina Col Ⅳ and the permeability of brain micrangium in cerebral ischemic rats with BMSC transplantation, and its mechanisms may be related to regulating the balance of MMP-9, especially by increasing the expression of TIMP-1.

Key words: cerebral ischemia, rats, rhubarb aglycone, bone marrow mesenchymal stem cells, blood brain barrier, matrix metalloproteinase

CLC Number: 

  • R285.5

Figure 1

Pathological changes of brain micrangium in rats in different groups at the twenty-eighth day (HE staining, ×200) A: Sham-operated group; B: Untreated group; C: Rhubarb aglycone group; D: Transplantation group; E: Combination group."

Table 1

Expressions of IgG, ColⅣ, TIMP-1 and activity of MMP-9 in brain of rats in different groups (x±s, IOD×10-2)"

Group n IgG ColⅣ MMP-9 TIMP-1
Sham-operated 6 13.85±2.08 42.71±8.86 24.32±6.29 22.25±4.26
Untreated
7 days 7 34.87±6.14 23.56±3.44 62.65±7.39 20.47±4.75
14 days 6 49.70±11.49□□ 15.79±2.46 64.43±9.37 18.44±2.19
28 days 6 53.00±7.57**□□ 15.59±1.83** 82.76±13.24**□□■■ 16.84±2.00
Rhubarb aglycone
7 days 7 20.92±8.74△△ 40.86±5.19△△ 48.56±12.79△ 46.25±11.13△△☆☆
14 days 7 21.40±4.22△△ 45.24±4.92△△ 51.90±24.38△☆ 24.91±3.70△△☆☆□□
28 days 6 32.32±8.98△△□■■ 39.18±7.48△△ 42.22±8.89△△ 30.64±5.01△△□□
Transplantation
7 days 7 28.86±3.91▲▲ 27.71±4.70▲▲☆☆ 50.91±8.16 35.87±5.72△△▲▲
14 days 6 20.08±5.91△△□ 32.54±4.30△△▲☆☆ 31.99±5.98△△▲▲□□ 42.37±8.93△△▲▲
28 days 6 22.92±4.93△△▲ 34.33±5.09△△☆ 39.18±10.79△△ 29.61±3.13△△□☆
Combination
7 days 7 25.20±8.70△△ 44.48±14.38△△ 48.95±20.45△ 35.88±6.87△△
14 days 6 27.68±10.72△△ 49.52±7.35△△ 32.48±7.37△△□□ 35.19±13.31△△
28 days 7 26.00±1.51△△ 45.27±8.13△△ 36.19±5.57△△□ 36.39±5.08△△

Figure 2

Expression of IgG in brain of rats in different groups at the twenty-eighth day (SABC staining, ×200) Sham-operated group; B: Untreated group; C: Rhubarb aglycone group; D: Transplantation group; E: Combination group."

Figure 3

Expression of Col Ⅳ in brain of rats in different groups at the twenty-eighth day (SABC staining, ×200) Sham-operated group; B: Untreated group; C: Rhubarb aglycone group; D: Transplantation group; E: Combination group."

Figure 4

Expression of MMP-9 in brain of rats in different groups at the twenty-eighth day (SABC staining, ×200) Sham-operated group; B: Untreated group; C: Rhubarb aglycone group; D: Transplantation group; E: Combination group."

Figure 5

Expression of TIMP-1 in brain of rats in different groups at the twenty-eighth day (SABC staining, ×200) Sham-operated group; B: Untreated group; C: Rhubarb aglycone group; D: Transplantation group; E: Combination group."

[1] Zhu JZ, Zhao JD, Miao ZN , et al. The empirical study of differentiation of bone marrow mesenchymal stem cells into cells of endothelial lineage in vitro[J]. Zhongguo Wei Xun Huan, 2005,9(6):409-412
祝建中, 赵基栋, 苗宗宁 , 等. 体外诱导骨髓间充质干细胞分化为血管内皮细胞的实验研究[J]. 中国微循环, 2005,9(6):409-412
[2] Hess DC, Hill WD, Martin-Studdard A , et al. Bone marrow as a source of endothelial cells and NeuN-expressing cells after stroke[J]. Stroke, 2002,33(5):1362-1368
doi: 10.1161/01.STR.0000014925.09415.C3
[3] Li JS, Liu K, Wang MH , et al. Modulation effect of naomaitong on gelatinase system after cerebral ischemia/reperfusion in rats[J]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2006,26(Ji Chu Li Lun Yan Jiu Te Ji):14-17
李建生, 刘轲, 王明航 , 等. 脑脉通对大鼠脑缺血/再灌注明胶酶系统调节作用的影响[J]. 中国中西医结合杂志, 2006,26(基础理论研究特辑):14-17
[4] Li JS, Liu JX, Liang SW , et al. The selecting of protective role of Rhubarb's effective parts in ischemic injury in rats[J]. Zhongguo Lao Nian Xue Za Zhi, 2004,24(11):1032-1034
doi: 10.3969/j.issn.1005-9202.2004.11.022
李建生, 刘敬霞, 梁生旺 , 等. 大黄有效部位保护大鼠脑缺血损伤作用的筛选研究[J]. 中国老年学杂志, 2004,24(11):1032-1034
doi: 10.3969/j.issn.1005-9202.2004.11.022
[5] Cao YJ, Cheng YB . The improvement and discussion of the model of focal cerebral ischemia/reperfusion with suture-occluded method in rats[J]. Zhongguo Ying Yong Sheng Li Xue Za Zhi, 2001,17(2):198-200
doi: 10.3969/j.issn.1000-6834.2001.02.025
曹勇军, 程彦斌 . 线栓法建立大鼠局灶性脑缺血/再灌注模型的改进与探讨[J]. 中国应用生理学杂志, 2001,17(2):198-200
doi: 10.3969/j.issn.1000-6834.2001.02.025
[6] Li PT, Ji H, Huang QF , et al. Study on Jiedu Tongluo Fang improving regeneration of neuronal protrusion after cerebral ischemic damage[J]. Shen Jing Jie Pou Xue Za Zhi, 2002,18(4):337-341
doi: 10.3969/j.issn.1000-7547.2002.04.012
李澎涛, 冀宏, 黄启福 , 等. 解毒通络方促进脑缺血损伤后神经元突起再生的研究[J]. 神经解剖学杂志, 2002,18(4):337-341
doi: 10.3969/j.issn.1000-7547.2002.04.012
[7] Li L, Huang RX, Zhang XY , et al. Changes in the structure and components of the brain microvascular basement membrane in reperfusion areas after focal cerebral ischemia in renovascular hypertensive stroke prone rats[J]. Zhonghua Lao Nian Yi Xue Za Zhi, 2000,19(5):364-367
doi: 10.1007/s11769-000-0028-3
李玲, 黄如训, 张小燕 , 等. 局部脑缺血再灌注病灶区脑微血管基底膜及其成分改变的实验研究[J]. 中华老年医学杂志, 2000,19(5):364-367
doi: 10.1007/s11769-000-0028-3
[8] Chen J, Weinstein PR, Graham SH . Attenuation of postischemic brain hypoperfusion and reperfusion injury by the cyclooxygenase-lipoxygenase inhibitor BW755C[J]. J Neurosurg, 1995,83(1):99-104
doi: 10.3171/jns.1995.83.1.0099
[9] Belayev L, Busto R, Zhao W , et al. Quantitative evaluation of blood-brain barrier permeability following middle cerebral artery occlusion in rats[J]. Brain Res, 1996,739(1-2):88-96
doi: 10.1016/S0006-8993(96)00815-3
[10] Hamann GF, Liebetrau M, Martens H , et al. Microvascular basal lamina injury after experimental focal cerebral ischemia and reperfusion in the rat[J]. J Cereb Blood Flow Metab, 2002,22(5):526-533
doi: 10.1097/00004647-200205000-00004
[11] Liu K, Li JS, Wang MH , et al. Relationship of changes in basement membrane of microvessels after cerebral ischemia/reperfusion and plasminogen activator system in aged rats[J]. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue, 2005,17(11):654-657
doi: 10.3760/j.issn:1003-0603.2005.11.005
刘轲, 李建生, 王明航 , 等. 老龄大鼠脑缺血再灌注微血管基底膜损伤变化及与纤溶酶原激活系的关系[J]. 中国危重病急救医学, 2005,17(11):654-657
doi: 10.3760/j.issn:1003-0603.2005.11.005
[12] Chen X, Li Y, Wang L , et al. Ischemic rat brain extracts induce human marrow stromal cell growth factor production[J]. Neuropathology, 2002,22(4):275-279
doi: 10.1046/j.1440-1789.2002.00450.x
[13] Kinnaird T, Stabile E, Burnett MS , et al. Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms[J]. Circ Res, 2004,94(5):678-685
doi: 10.1161/01.RES.0000118601.37875.AC
[14] Li Y, Chopp M, Chen J , et al. Intrastriatal transplantation of bone marrow nonhematopoietic cells improves functional recovery after stroke in adult mice[J]. J Cereb Blood Flow Metab, 2000,20(9):1311-1319
doi: 10.1097/00004647-200009000-00006
[15] Aoki T, Sumii T, Mori T , et al. Blood-brain barrier disruption and matrix metalloproteinase-9 expression during reperfusion injury: mechanical versus embolic focal ischemia in spontaneously hypertensive rats[J]. Stroke, 2002,33(11):2711-2717
doi: 10.1161/01.STR.0000033932.34467.97
[1] Na Wu , Lu Song , Xin-xin Yang, Jiang-lei Wei , Zhen-guo Liu. Effects of Chinese herbal medicine Tianqi Pingchan Granule on G protein-coupled receptor kinase 6 involved in the prevention of levodopa-induced dyskinesia in rats with Parkinson disease. Journal of Chinese Integrative Medicine, 2012, 10(9): 1018-1024.
[2] Lawrence A. Olatunji, Taofeek O. Usman, Joseph O. Adebayo, Victoria A. Olatunji . Effects of aqueous extract of Hibiscus sabdariffa on renal Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities in Wistar rats. Journal of Chinese Integrative Medicine, 2012, 10(9): 1049-1055.
[3] Dhirender Kaushik, Ajay Kumar, Pawan Kaushik, Avatar C. Rana. Anticonvulsant activity of alcoholic extract of bark of Pinus roxburghii Sarg. Journal of Chinese Integrative Medicine, 2012, 10(9): 1056-1060.
[4] Chan Chen, Chang-xun Chen, Xi-min Wu, Rui Wang, Yi-ming Li. Effects of extracts of Radix Scrophulariae on blood pressure in spontaneously hypertensive rats and the underlying mechanisms. Journal of Chinese Integrative Medicine, 2012, 10(9): 1009-1017.
[5] Jian-sheng Li, Ya Li, Su-yun Li, Yuan-yuan Wang, Li Deng, Yan-ge Tian, Su-li Jiang , Ying Wang. Long-term effects of Tiaobu Feishen therapies on systemic and local inflammation responses in rats with stable chronic obstructive pulmonary disease. Journal of Chinese Integrative Medicine, 2012, 10(9): 1039-1048.
[6] Lu Liu, Ying Gao. Study on the correlation between traditional Chinese medicine syndrome and short-term prognosis of ischemic stroke using logistic regression model and repeated-measures analysis of variance. Journal of Chinese Integrative Medicine, 2012, 10(9): 983-990.
[7] Karuna A. Talpate, Uma A. Bhosale, Mandar R. Zambare. Clitorea ternatea, a herb from Indian folklore, improves streptozotocin-induced diabetes and diabetes-induced cognitive decline in rats. Journal of Chinese Integrative Medicine, 2012, 10(8): 939-947.
[8] Di Li, Guan-liang Wang, Meng-ya Shan, Jia-han Liu, Lin Wang, De-zeng Zhu. Effects of ursolic acid on c-Cbl-associated protein expression in 3T3-L1 adipocytes with insulin resistance. Journal of Chinese Integrative Medicine, 2012, 10(8): 886-893.
[9] Samuel Joshua Pragasam, Vachana Murunikara, Evan Prince Sabina, Mahaboobkhan Rasool. Antiperoxidative potential of p-coumaric acid, a common dietary phenol, in adjuvant-induced arthritis in rats. Journal of Chinese Integrative Medicine, 2012, 10(8): 932-938.
[10] Zi-hui Li, Jian Wang, Rong-lin Cai, You-wen Wang, Jian-peng Hu. Establishment and evaluation of a rat model of ulcerative colitis with syndrome of dampness stagnancy due to spleen deficiency. Journal of Chinese Integrative Medicine, 2012, 10(8): 918-924.
[11] Meng Li, Ling Hu, Rong-lin Cai, Zi-jian Wu, Ke-ming Wang. Effects of electro-acupuncture at PC6 and BL15 on nerve electrical activity in spinal dorsal root and norepinephrine and dopamine contents in paraventricular nucleus of hypothalamus in rats with acute myocardial ischemia. Journal of Chinese Integrative Medicine, 2012, 10(8): 874-879.
[12] Xin-min Li, Hui Chen, Yan-yan Ren, Yan-li Lu. Effects of Chinese herbal medicine Xifeng Capsule on multidrug resistance-associated protein 1 expression in hippocampus and cortex of rats with lithium-pilocarpine-induced epilepsy. Journal of Chinese Integrative Medicine, 2012, 10(8): 911-917.
[13] Hong Wang , Jing-tian Ou , Xin Zhao , Ying Guoz , Hao-ping Mao. Vasodilator effect of oroxylin A on thoracic aorta isolated from rats. Journal of Chinese Integrative Medicine, 2012, 10(8): 880-885.
[14] C. Mouli Kalla, Vijaya Tartte, Dattatreya Rao Sirpurkar. Effectiveness of flavonoid-rich leaf extract of Acalypha indica in reversing experimental myocardial ischemia: biochemical and histopathological evidence. Journal of Chinese Integrative Medicine, 2012, 10(7): 784-792.
[15] Feng Xin-ying, Zhu Min, Zhang Qi-qi, Chen Yi-ping, Li Wen-wei. Selective protection of nigral dopaminergic neurons by echinacoside in a rat model of Parkinson disease induced by rotenone. Journal of Chinese Integrative Medicine, 2012, 10(7): 777-783.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] Jin-zhou Tian, Jing Shi, Xin-qing Zhang, Qi Bi, Xin Ma, Zhi-liang Wang, Xiao-bin Li, Shu-li Shen, Lin Li, Zhen-yun Wu, Li-yan Fang, Xiao-dong Zhao, Ying-chun Miao, Peng-wen Wang, Ying Ren, Jun-xiang Yin, Yong-yan Wang, Beijing United Study Group on MCI of the Capital Foundation of Medical Developments. An explanation on "guiding principles of clinical research on mild cognitive impairment (protocol)". Journal of Chinese Integrative Medicine, 2008, 6(1): 15-21
[2] Yi-ting He, Qing-lin Zha, Jian-ping Yu, Yong Tan, Cheng Lu, Ai-ping Lv. Principal factor analysis of symptoms of rheumatoid arthritis and their correlations with efficacy of traditional Chinese medicine and Western medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 32-36
[3] Jun Cai, Hua Wang, Sheng Zhou, Bin Wu, Hua-rong Song, Zheng-rong Xuan. Effect of Sijunzi Decoction and enteral nutrition on T-cell subsets and nutritional status in patients with gastric cancer after operation: A randomized controlled trial. Journal of Chinese Integrative Medicine, 2008, 6(1): 37-40
[4] Wei Zhang, Xiang-feng Lu, Xiao-mei Zhang, Jian-jun Wu, Liang-duo Jiang. A rat model of pulmonary fibrosis induced by infusing bleomycin quickly through tracheal intubation. Journal of Chinese Integrative Medicine, 2008, 6(1): 60-67
[5] A-gao Zhou, Yong Zhang, Gang Kui, De-Yun Kong, Hai-liang Ge, Qiu-hua Ren, Jia-rong Dong, Sheng Hong, Xu-ming Mao, Yin Wang, Hui-zheng Zhang, Shu-jun Wang. Influence of traditional Chinese compound recipes with different efficacy on body weight, tumor weight and immune function in H22 cancer-bearing mice. Journal of Chinese Integrative Medicine, 2008, 6(1): 77-82
[6] Guo-hong Yuan, Xiao-jing Pang, He-chao Ma. Synergic effects of Danggui Buxue Decoction in reducing toxicity of cytoxan in tumor-bearing mice. Journal of Chinese Integrative Medicine, 2008, 6(1): 83-88
[7] Li Zhou, Hong-xing Zhang, Ling-guang Liu, Wen-jun Wan. Effect of electro-acupuncture at Fenglong (GV 16) on nitric oxide and endothelin in rats with hyperlipidemia. Journal of Chinese Integrative Medicine, 2008, 6(1): 89-92
[8] Jin-zhou Tian, Jing Shi, Xin-qing Zhang, Qi Bi, Xin Ma, Zhi-liang Wang, Xiao-bin Li, Shu-li Shen, Lin Li, Zhen-yun Wu, Li-yan Fang, Xiao-dong Zhao, Ying-chun Miao, Peng-wen Wang, Ying Ren, Jun-xiang Yin, Yong-yan Wang, Beijing United Study Group on MCI of the Capital Foundation of Medical Developments. Guiding principles of clinical research on mild cognitive impairment (protocol). Journal of Chinese Integrative Medicine, 2008, 6(1): 9-14
[9] Xin-jun Wang, Ling-ling Wang . A mechanism of endogenous opioid peptides for rapid onset of acupuncture effect in treatment of depression. Journal of Chinese Integrative Medicine, 2010, 8(11): 1014-1017
[10] Bo Wang , Wei Yan , Li-hui Hou, Xiao-ke Wu. Disorder of Tiangui (kidney essence) and reproductive dysfunction in patients with polycystic ovary syndrome. Journal of Chinese Integrative Medicine, 2010, 8(11): 1018-1022
[an error occurred while processing this directive]