Dissertation > Medicine, health > Pharmacy > Pharmacology

Study on the Effect and Mechanism of Oral Arginine in Improving Linear Growth of Long Bones

Author JiangMingYu
Tutor CaiDePei
School Fudan University
Course Traditional Chinese Medicine
Keywords Arginine Nitric oxide synthase Nitric oxide Growth Hormone Undersized Histomorphometry Histomorphological Ultrastructure
Type Master's thesis
Year 2011
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Objective: (1) clinical observation and evaluation of oral L-arginine (L-arginine, L-arginine) to promote the role of children with short stature height growth. (2) through animal experiments to study the role of oral L-arginine to promote linear growth of the long bones, and nitric oxide (NO), the angle of the signal transduction pathway of gene expression from the hypothalamic - pituitary growth axis and explore its mechanism of action to promote the linear growth of long bones. (3) Observation of oral arginine the toxic effects that may exist in the important organs of the experimental animals in order to evaluate the safety of the treatment. Methods: (1) 45 cases of children with short stature given oral L-arginine, outpatient follow-up observation, the height of the detector before and after treatment, bone width (BW), bone mineral content (BMC) and bone mineral density (BMD). Using its own paired t test was used for statistical analysis. (2) to 5-week-old male SD rats as experimental subjects, fed saline control group, the intervention group were fed L-arginine, for 4 weeks. The method of using bone histomorphometry were measured tibial growth plate width (GP) and mineral apposition rate (MAR), the percentage of femoral trabecular bone volume (BV / TV,%), osteoblast area (Ob.S / BS,% quantitative real-time - polymerase chain reaction (Real-time PCR) detection) and osteoclast area (Oc.S / BS,%); levels of growth hormone (GH) concentrations were measured by radioimmunoassay; hypothalamic neuronal oxidative Nitrogen oxide synthase (nNOS), soluble guanylate cyclase α1 (sGCα1), soluble guanylate cyclase β1 (sGCβ1), cGMP-dependent protein kinase Ⅱ (PKG Ⅱ), growth hormone releasing hormone (GHRH), somatostatin (SS) and pituitary growth hormone (GH) gene expression levels; hypothalamic of of nNOS, sGCal and sGCβ1 the protein expression level was determined by Western blot (Western blot). Between the two groups were compared using t-test was used for statistical analysis. (3) 5-week-old SD rats as experimental subjects fed saline control group, the intervention group were fed arginine for 12 weeks. Observed under light microscope and transmission electron microscope each group of rat cerebral cortex, hypothalamus, pituitary, heart, liver, kidney tissue morphology and ultrastructure. Results: (1) L-arginine oral treatment, children with short stature growth rate (GV) and height standard deviation score (SDS) improved significantly (P lt; 0.05); bone mineral content and bone mineral density was significantly increased (P lt; 0.05). (2) the width of the growth plate of the tibia and femur of the intervention group osteoblasts area was significantly increased (P lt; 0.05); serum GH concentrations were significantly increased (P lt; 0.05): the hypothalamus of nNOS in sGCal gene and protein expression were significantly increased (P lt; 0.05), SS gene expression was significantly lowered (P lt; 0.05), pituitary GH gene expression was significantly increased (P lt; 0.01). (3) the intervention group rat cerebral cortex, hypothalamus, pituitary, heart, liver, and kidney tissue morphology and ultrastructure of the control group showed no significant differences. Conclusions: (1) short stature in children with oral arginine therapy Height growth accelerated increase in bone mineral content and bone mineral density, and no significant adverse reactions. (2) oral arginine, at the same time to promote growth in children with short stature height, but also make the bone metabolism in a positive state of equilibrium. (3) oral arginine by nNOS-NO-sGC-cGMP pathway gene expression of hypothalamic SS lowered pituitary GH gene upregulation, which significantly increased the synthesis and secretion of pituitary GH. (4) oral arginine by promoting the synthesis of pituitary GH secretion increased serum GH levels were significantly higher, caused long bone growth plate width increase the active osteoblast function, thus significantly promote linear growth of long bones. The dose and duration of L-arginine (5) of this topic are in the safe range of vital organs without apparent side effects.

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