Ghrelin及其受体在大鼠中枢神经系统的分布特征及比较

Distributional characteristics and comparison of ghrelin and its receptor in the brain of rats

目的观察ghrelin及其受体生长激素促分泌素受体(GHS-R)在大鼠中枢的分布特征及表达水平。方法采用免疫组织化学和图像分析方法观察ghrelin和GHS-R在大鼠中枢的分布特征及在与消化功能相关脑区的表达水平。结果 Ghrelin与GHS-R免疫阳性表现为细胞膜染色,部分有细胞质着色,在中枢的海马(HIP)、弓状核(ARC)、室旁核(PVN)、杏仁核、延髓、小脑等部位均有表达。在与消化功能密切相关的脑区,二者表达量较多。Ghrelin在下丘核的PVN和下丘脑外侧区(LH)表达最多,免疫反应阳性细胞数分别为116.31±7.76和107.02±8.80,明显高于ARC(75.12±5.59)、下丘脑背内侧核(DMH)(56.84±7.07)和下丘脑腹内侧核(VMH)(62.54±6.93),差异有统计学意义(P<0.05);在HIP的CA3区表达最多,免疫反应阳性细胞数为123.20±11.17,明显高于CA1区(67.46±6.93)、CA2区(37.91±5.21)和CA4区(59.96±6.73),差异有统计学意义(P<0.05)。GHS-R在下丘脑的PVN和ARC表达最多,免疫反应阳性细胞数分别为111.06±11.80和97.06±10.37,明显高于LH(74.70±6.04)、DMH(58.65±7.28)和VMH(48.24±6.58),差异有统计学意义(P<0.05);在HIP的CA3和CA4区表达最多,免疫反应阳性细胞数分别为103.79±9.23和86.48±7.25,明显高于CA1区(51.16±6.56)和CA2区(43.39±5.11),差异有统计学意义(P<0.05)。Ghrelin和GHS-R在杏仁内侧核均有强阳性表达,免疫反应阳性细胞数分别为140.22±9.07和115.66±7.35,明显高于其他核区,差异有统计学意义(P<0.05)。结论 Ghrelin可能作为神经调节递质广泛作用于中枢各脑区,尤其是HIP、杏仁核、下丘脑等与消化功能相关的脑区,通过其受体GHS-R发挥各种生理调节作用。

Objective To investigate the distribution characteristics of ghrelin and its receptor growth hormone secretagogue receptor（ GHS-R） in the central nervous system of rats. Methods Immunohistochemistry and image analysis were applied to observe the distribution characteristic of ghrelin and GHS-R in the center and expression level in the nucleus related to the digestive function. Results Ghrelin and GHS-R immunopositive expression showed that the cell membrane was stained and some cytoplasm was stained. The ghrelin and GHS-R were positive expression in hippocamp（ HIP）,arcuate nucleus（ ARC）,paraventricular nucleus（ PVN）,amygdale,medulla and cerebellum. The expression of ghrelin and GHS-R in brain which related to the digestive function were more. The expression of ghrelin in PVN of nucleus of inferior colliculus and lateral hypothalamic area（ LH） were the most; the number of positive cell was 116. 31 ± 7. 76 and 107. 02 ± 8. 80,respectively; the number of the positive cell in the PVN of nucleus of inferior colliculus and lateral hypothalamic area（ LH） was significantly higher than that in ARC（ 75. 12 ± 5. 59）,dorsomedial hypothalamic nucleus（ DMH）（ 56. 84 ± 7. 07） and ventromedial hypothalamic nucleus（ VMH）（ 62. 54 ± 6. 93）（ P〈0. 05）. The expression of ghrelin in CA3 region of HIP was the most; the number of positive cell in CA3 region（ 123. 20 ± 11. 17） was significantly higher than that in CA1（ 67. 46 ± 6. 93）,CA2（ 37.91 ±5.21）,CA4（ 59.96 ±6.73） region（ P〈0.05）. The expression of GHS-R in PVN and ARC of hypothalamic was the most; the number of positive cell was 111. 06 ± 11. 80,97. 06 ± 10. 37,respectively; the number of positive cell in PVN and ARC of hypothalamic was significantly higher than that in LH（ 74. 70 ± 6. 04）,DMH（ 58. 65 ± 7. 28）,VMH（ 48. 24 ±6. 58）（ P〈0. 05）. The expression of GHS-R in CA3 and CA4 region of HIP was the most; the number of positive cell was103. 79 ± 9. 23,86. 48 ± 7. 25,respectively; the number of positive cell in CA3 and CA4 region was significantly higher than that in CA1（ 51. 16 ± 6. 56） and CA2（ 43. 39 ± 5. 11） region（ P〈0. 05）. Ghrelin and GHS-R had strong positive expression in the medial amygdaloid nucleus; the number of positive cell was 140. 22 ± 9. 07 and 115. 66 ± 7. 35 respectively and the number of positive cell was significantly higher than that in other region（ P〈0. 05）. Conclusions Ghrelin may act as a neuromodulator in the each brain region of central,especially in the HIP,amygdala,hypothalamus and other brain region which are associated with the digestive function. Ghrelin can regulate physiological function through GHS-R in these encephalic regions.