Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin 682 022, Kerala, India.
Eur J Pharmacol. 2013 Sep 5;715(1-3):154-63. doi: 10.1016/j.ejphar.2013.05.028. Epub 2013 Jun 6.
Liver is one of the major organs in vertebrates and hepatocytes are damaged by many factors. The liver cell maintenance and multiplication after injury and treatment gained immense interest. The present study investigated the role of Gamma aminobutyric acid (GABA) and serotonin or 5-hydroxytryptamine (5-HT) coupled with chitosan nanoparticles in the functional regulation of Gamma aminobutyric acid B and 5-hydroxy tryptamine 2A receptors mediated cell signaling mechanisms, extend of DNA methylation and superoxide dismutase activity during enhanced liver cell proliferation. Liver injury was achieved by partial hepatectomy of male Wistar rats and the GABA and 5-HT chitosan nanoparticles treatments were given intraperitoneally. The experimental groups were sham operated control (C), partially hepatectomised rats with no treatment (PHNT), partially hepatectomised rats with GABA chitosan nanoparticle (GCNP), 5-HT chitosan nanoparticle (SCNP) and a combination of GABA and 5-HT chitosan nanoparticle (GSCNP) treatments. In GABA and 5-HT chitosan nanoparticle treated group there was a significant decrease (P<0.001) in the receptor expression of Gamma aminobutyric acid B and a significant increase (P<0.001) in the receptor expression of 5-hydroxy tryptamine 2A when compared to PHNT. The cyclic adenosine monophosphate content and its regulatory protein, presence of methylated DNA and superoxide dismutase activity were decreased in GCNP, SCNP and GSCNP when compared to PHNT. The Gamma aminobutyric acid B and 5-hydroxy tryptamine 2A receptors coupled signaling elements played an important role in GABA and 5-HT chitosan nanoparticles induced liver cell proliferation which has therapeutic significance in liver disease management.
肝脏是脊椎动物的主要器官之一，肝细胞受到许多因素的损伤。受伤和治疗后的肝维持和增殖引起了广泛关注。本研究探讨了γ-氨基丁酸（GABA）和血清素或 5-羟色胺（5-HT）与壳聚糖纳米颗粒偶联在调节γ-氨基丁酸 B 和 5-羟色胺 2A 受体介导的细胞信号转导机制、DNA 甲基化程度和超氧化物歧化酶活性中的作用，从而增强肝细胞增殖。通过部分肝切除术对雄性 Wistar 大鼠造成肝损伤，并通过腹腔内给予 GABA 和 5-HT 壳聚糖纳米颗粒治疗。实验组包括假手术对照组（C）、未治疗的部分肝切除大鼠（PHNT）、GABA 壳聚糖纳米颗粒治疗组（GCNP）、5-HT 壳聚糖纳米颗粒治疗组（SCNP）和 GABA 和 5-HT 壳聚糖纳米颗粒联合治疗组（GSCNP）。在 GABA 和 5-HT 壳聚糖纳米颗粒治疗组中，与 PHNT 相比，γ-氨基丁酸 B 受体的表达显著降低（P<0.001），5-羟色胺 2A 受体的表达显著增加（P<0.001）。与 PHNT 相比，GCNP、SCNP 和 GSCNP 中的环磷酸腺苷含量及其调节蛋白、甲基化 DNA 的存在和超氧化物歧化酶活性降低。GABA 和 5-HT 壳聚糖纳米颗粒诱导的肝细胞增殖中，GABA B 和 5-HT 2A 受体偶联的信号转导元件发挥了重要作用，这对肝脏疾病的治疗管理具有重要意义。
