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Journal of Chinese Integrative Medicine ›› 2012, Vol. 10 ›› Issue (9): 1018-1024.doi: 10.3736/jcim20120911

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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

Na Wu1, Lu Song1, Xin-xin Yang1, Jiang-lei Wei2, Zhen-guo Liu1()   

  1. 1. Department of Neurology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
    2. Department of Emergency, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
  • Received:2012-02-12 Accepted:2012-02-28 Online:2012-09-20 Published:2018-09-15
  • Contact: Zhen-guo Liu

Objective: To investigate the effects of Tianqi Pingchan (TQPC) Granule, a compound traditional Chinese herbal medicine with antitremor activity, on levodopa-induced dyskinesia and the expression of G protein-coupled receptor kinase 6 (GRK6) in rats with Parkinson disease (PD).

Methods: The hemi-Parkinsonian rat model was established by sterotaxically injecting 6-hydroxydopa (6-OHDA) to the right medial forebrain bundle. Rats with PD were randomly divided into 5 groups with 5 in each. PD group was intraperitoneally injected with vitamin C; levodopa group was intraperitoneally injected with levodopa and benserazide; low-, medium- and high-dose TQPC Granule groups were intraperitoneally injected with levodopa and benserazide and treated with different dosages of TQPC Granule by gavage for 29 d. Another 5 rats were served as control with sham-operation. The behaviors of rats were observed and classified with abnormal involuntary movement (AIM) score. The expression of GRK6 in the striate of rats was detected by immunohistochemical method and Western blotting.

Results: AIM score was increased and the expression of GRK6 protein in lesion side was decreased after the long-tern treatment with levodopa and benserazide in rats. The AIM scores of rats with PD were decreased after TGPC Granule treatment. Immunohistochemical results showed that the number of GRK6-positive cells in medium- and high-dose TQPC Granule groups was increased as compared to that in the levodopa group (P<0.05). The expression level of GRK6 protein was increased in medium-dose TQPC Granule group when compared with the levodopa group (P<0.01), which was observed by Western blotting.

Conclusion: TGPC Granule can increase the expression of GRK6, inhibit the increase of AIM, and reduce the incidence of levodopa-induced dyskinesia in rats with PD.

Key words: Parkinson’s disease;, levodopa, dyskinesia, drugs, Chinese herbal, G-protein-coupled receptor kinase 6, rats

Table 1

AIM scores in different groups ($\overline{x}$±s)"

Time Group n AIM scores
Orolingual Upper limb Axial Locomotor
2 d Levodopa 5 1.44±0.18 1.51±0.22 2.49±0.17 2.67±0.28
Low-dose TQPC Granule 5 1.51±0.17 1.58±0.19 2.42±0.16 2.62±0.23
Medium-dose TQPC Granule 5 1.40±0.19 1.56±0.28 2.51±0.22 2.71±0.34
High-dose TQPC Granule 5 1.42±0.24 1.62±0.26 2.38±0.15 2.62±0.23
8 d Levodopa 5 1.82±0.17 1.93±0.20 2.71±0.41 3.20±0.25
Low-dose TQPC Granule 5 1.89±0.21 1.91±0.19 2.76±0.41 3.16±0.20
Medium-dose TQPC Granule 5 1.56±0.18 1.76±0.16 2.58±0.29 2.93±0.19
High-dose TQPC Granule 5 1.51±0.22 1.67±0.22 2.42±0.24 2.60±0.06
15 d Levodopa 5 2.11±0.22 2.18±0.15 2.93±0.28 3.36±0.28
Low-dose TQPC Granule 5 1.84±0.17 2.09±0.12 2.71±0.37 3.09±0.24
Medium-dose TQPC Granule 5 1.47±0.14 1.71±0.22 2.69±0.24 2.84±0.19
High-dose TQPC Granule 5 1.33±0.11 1.51±0.22 2.38±0.20 2.58±0.15
22 d Levodopa 5 2.40±0.37 2.56±0.16 3.18±0.15 3.38±0.29
Low-dose TQPC Granule 5 1.96±0.20 2.13±0.14 2.62±0.28 3.11±0.21
Medium-dose TQPC Granule 5 1.49±0.13 1.69±0.20 2.29±0.13 2.67±0.11
High-dose TQPC Granule 5 1.29±0.13 1.49±0.23 2.24±0.18 2.53±0.15
29 d Levodopa 5 2.36±0.36 2.60±0.13 3.16±0.13 3.47±0.23
Low-dose TQPC Granule 5 2.04±0.13 2.13±0.20 2.76±0.26 3.24±0.14
Medium-dose TQPC Granule 5 1.33±0.21 1.67±0.18 2.33±0.16 2.56±0.14
High-dose TQPC Granule 5 1.20±0.09 1.53±0.21 2.11±0.78 2.29±0.10

Table 2

Effects of different doses of Tianqi Pingchan Granule on striatal GRK6 expression in rats with levodopa-induced PD"

Group n IOD (×103)
Lesioned side Unlesioned side
Sham 5 6.20±0.55 6.03±0.59
PD 5 4.54±0.85** 6.01±0.72
Levodopa 5 3.53±0.71 5.90±1.51
Low-dose TQPC Granule 5 4.17±1.20 5.72±1.30
Medium-dose TQPC Granule 5 4.31±0.95 6.35±1.26
High-dose TQPC Granule 5 4.88±1.24 6.03±1.14

Figure 1

Immunohistochemical method confirmed the effects of different doses of TQPC Granule on GRK6 expression in striatum of rats with PD (light microscopy, ×400) 1: Sham group; 2: PD group; 3: Levodopa group; 4: Low-dose TQPC Granule group; 5: Medium-dose TQPC Granule group; 6: High-dose TQPC Granule group. U: Unlesioned side; L: Lesioned side; PD: Parkinson disease; TQPC: Tianqi Pingchan; GRK6: G protein coupled receptor kinase 6."

Figure 2

Western blot results confirmed the effects of different doses of TQPC Granule on GRK6 expression in striatum of rats with PD 1, 2: Sham group; 3, 4: PD group; 5, 6: Levodopa group; 7, 8: Low-dose TQPC Granule group; 9, 10: Medium-dose TQPC Granule group; 11, 12: High-dose TQPC Granule group; 1, 3, 5, 7, 9, 11: Unlesioned side; 2, 4, 6, 8, 10, 12: Lesioned side. PD: Parkinson disease; TQPC: Tianqi Pingchan; GRK6: G protein coupled receptor kinase 6."

[1] Liu ZG, Qi C . Motor complications of Parkinson’s disease and its treatment strategies[J]. Zhonghua Yi Xue Za Zhi, 2009,89(35):2516-2519
刘振国, 戚辰 . 帕金森病运动并发症及其治疗策略[J]. 中华医学杂志, 2009,89(35):2516-2519
[2] Obeso JA, Rodriguez-Oroz M, Marin C, Alonso F, Zamarbide I, Lanciego JL, Rodriguez-Diaz M . The origin of motor fluctuations in Parkinson’s disease: importance of dopaminergic innervation and basal ganglia circuits[J]. Neurology, 2004,62(1 Suppl 1):S17-S30
doi: 10.1212/WNL.62.10.17A
[3] Kovoor A, Seyffarth P, Ebert J, Barghshoon S, Chen CK, Schwarz S, Axelrod JD, Cheyette BN, Simon MI, Lester HA, Schwarz J . D2 dopamine receptors colocalize regulator of G-protein signaling 9-2(RGS9-2) via the RGS9 DEP domain, and RGS9 knock-out mice develop dyskinesias associated with dopamine pathways[J]. J Neurosci, 2005,25(8):2157-2165
doi: 10.1523/JNEUROSCI.2840-04.2005
[4] DeWire SM, Ahn S, Lefkowitz RJ, Shenoy SK . β-arrestins and cell signaling[J]. Annu Rev Physiol, 2007, 69483-510
[5] Gurevich EV, Gurevich VV . Arrestins: ubiquitous regulators of cellular signaling pathways[J]. Genome Biol, 2006,7(9):236
doi: 10.1186/gb-2006-7-9-236
[6] Wu N, Yang XX, Song L, Liu ZG . Relationship between G protein-coupled receptor kinase 6 and N-methyl-D-aspartate receptor in the mechanism study underlying motor complications in Parkinson’s disease[J]. Zhonghua Lao Nian Yi Xue Za Zhi, 2011,30(4):327-331
吴娜, 杨新新, 宋璐, 刘振国 . 帕金森病运动并发症发生机制中G蛋白偶联受体激酶6与N-甲基-D-天冬氨酸受体关系的研究[J]. 中华老年医学杂志, 2011,30(4):327-331
[7] Ba MW, Liu ZG, Kong M, Yang HQ, Chen SD, Lu GQ . The establishment and evaluation of a rat model of levodopa-induced dyskinesia[J]. Shanghai Jiao Tong Da Xue Xue Bao Yi Xue Ban, 2006, 26810-812
巴茂文, 刘振国, 孔敏, 杨红旗, 陈生弟, 陆国强 . 左旋多巴诱发帕金森病大鼠异动症模型的建立和评价[J]. 上海交通大学学报(医学版), 2006, 26810-812
[8] Bao XM. The rat brain in stereotaxic coordinates[M]. Beijing: People’s Medical Publishing House, 2005, 16-35
包新民 . 大鼠脑立体定位图谱[M]. 北京: 人民卫生出版社, 2005, 16-35
[9] Ba MW, Liu ZG, Kong M, Chen SD, Lu GQ . Relationship between motor complications of Parkinson’s disease and phosphorylated GIuR1Ser845[J]. Zhonghua Shen Jing Ke Za Zhi, 2006,39(12):822-826
巴茂文, 刘振国, 孔敏, 陈生弟, 陆国强 . 帕金森病运动并发症与谷氨酸受体亚型GluR1Ser845磷酸化关系的实验研究[J]. 中华神经科杂志, 2006,39(12):822-826
[10] Kong M, Ba MW, Liu ZG . Research progress in motor complications of Parkinson’s disease[J]. Zhonghua Yi Xue Za Zhi, 2009,89(3):210-212
孔敏, 巴茂文, 刘振国 . 帕金森病运动并发症的研究进展[J]. 中华医学杂志, 2009,89(3):210-212
[11] Nanjing University of Chinese Medicine. Dictionary of traditional Chinese drugs.2nd ed[M]. Shanghai: Shanghai Scientific and Technical Publishers, 2006, 326-2086
南京中医药大学. 中药大辞典.第2版[M]. 上海: 上海科学技术出版社, 2006, 326-2086
[12] Yuan CX, Ye Q, Wang J, Zhang Y, Yuan CG . Effects of traditional Chinese herbal medicine on the neurobehavioral manifestations and the activity of dopamine D2 receptor in corpora striatum of rats with levodopa-induced dyskinesias[J]. J Chin Integr Med, 2008,6(10):1024-1028
袁灿兴, 叶青, 王洁, 张燕, 袁崇刚 . 滋补肝肾、通络解毒中药对异动症大鼠行为学及纹状体多巴胺D2受体活性的影响[J]. 中西医结合学报, 2008,6(10):1024-1028
[13] Zhang QJ, Zhang YY, Huang WY . Traditional Chinese medicine in treatment of Parkinson’s disease[J]. J Chin Integr Med, 2004,2(1):75-77
张秋娟, 张云云, 黄文燕 . 中医药治疗帕金森病的思路与方法[J]. 中西医结合学报, 2004,2(1):75-77
[14] Calabresi P, Giacomini P, Centonze D, Bernardi G . Levodopa-induced dyskinesia: a pathological form of striatal synaptic plasticity? Ann Neurol. 2000; 47(4 Suppl 1):S60-S68.
[15] Gurevich VV, Gurevich EV . The structural basis of arrestin-mediated regulation of G-protein-coupled receptors[J]. Pharmacol Ther, 2006,110(3):465-502
doi: 10.1016/j.pharmthera.2005.09.008
[16] Kohout TA, Lin FS, Perry SJ, Conner DA, Lefkowitz RJ . β-Arrestin 1 and 2 differentially regulate heptahelical receptor signaling and trafficking[J]. Proc Natl Acad Sci U S A, 2001,98(4):1601-1606
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