Experimental Study On Different Dosage L-arginine To The Osteoporosis Effect Of The Emasculate Rats

Objective:Establish an osteoporosis model of emasculate rats,to explore the influence of different dosage L-arginine on the blood biochemistry and bone metabolism changes to osteoporosis rats, and Screen effective dosage to cure osteoporosis,Explore the Monitoring indicators for the clinical dosage of L-arg.Method:(1) Divide 50 female rats of 3 months old into sham-operated (Sham group) including 10 rats and ovariectomy group (OVX group) including 40 rats. Excise bilateral ovaries to the OVX group. Make vagina cast-off cells smear for 3 consecutive days after the operation. The ones without comification mean that the bilateral ovaries are completely excised, or else it won't be used. For the Sham group, open their abdominal cavity and bare the bladder, excise a few adipose tissues from the side. After the operation, normally feed them for 12 weeks. (2) After 12 weeks, randomly select 10 rats from the OVX group and measure the bone mineral density (BDM) of lumbar vertebra. Compare it to the Sham group to judge whether the osteoporosis model is successfully established. (3) When the osteoporosis model is successfully established, randomly divide the OVX group into 4 groups:Osteoporosis group (OP group), low dosage L-arginine group (LL-Arg group), middle dosage L-arginine group (ML-Arg group) and high dosage L-arginine group (HL-Arg group),10 rats each group; 10 rats of Sham group; hypodermic inject normal saline to Sham group and OP group; hypodermic inject different dosages of L-Arg to the other three groups (0.25mg/kg,0.5mg/kg.d,1.5mg/kg.d). (4) Measure the lumbar vertebra bone mineral density of every group 12 weeks after the injection and compare them; get blood from the inferior vena cava and measure the Ca, P, alkaline phosphatase (ALP), Osteocalcin (OCN) potency and nitric oxide (NO) level, and compare the changes of blood biochemistry; take some tissue from the right thighbone and undertake morphologic observation.Results:(1) After the rats are castrated for 12 weeks, the BMD of the OVX group drops compared to the Sham group (P<0.05); make sure the osteoporosis model of Castrated rats is successfully established. (2) 12 weeks after the injection:①compared to the Sham group, the BMD of the OP group drops (P<0.05); and the BDM of the LL-Arg group and ML-Arg group is higher than the OP group (P<0.05); the BDM of HL-Arg group has no difference with the OP group (P>0.05).②Ca content:the Ca content of the LL-Arg group and the ML-Arg group is lower than the OP group (P<0.05); there is no significance difference between the OP group and the Sham group and the HL-Arg group (P>0.05);③P content:the content of the LL-Arg group and the ML-Arg is higher than the OP group; the content of the HL-Arg group is lower than the OP group (P<0.05); There is no significance difference between the OP group and the Sham group (P>0.05);④ALP value: compared to the Sham group, the serum ALP of the OP group rises (P<0.05), the value of the ML-Arg group and HL-Arg group drops compared to the OP group (P<0.05); and the ALP value of the LL-Arg group is of no significant difference with the OP group;⑤OCN value:compared to the Sham group, the blood OCN of the OP group rises (P<0.05); the value of LL-Arg group and the HL-Arg group rises compared to the OP group (P<0.05); and there is no significant difference between the ML-Arg group and the OP group (P>0.05).⑥Serum NO level:compared to the Sham group, the serum NO level of the OP group drops (P<0.05); the serum NO level of LL-Arg group, ML-Arg group and HL-Arg group are obviously higher than the OP group, and the difference has statistical meaning (P<0.05, P<0.01, P<0.01);⑦The morphology result of bone tissue shows:on the aspects of bone trabecula numbers, continuity and so on, the LL-Arg group, ML-Arg group and the Sham group is obviously better than the OP group, and the HL-Arg group is equal to the OP group.Conclusion:(1) Exogenous L-Arg can enhance the serum NO level. (2) L-Arg with low and middle dosage may enhance the bone density of osteoporosis rats, increases the bone trabecula quantity and continuity, and prevent and cure the osteoporosis after menopause. (3) Although high dose L-Arg may raise the blood serum NO level, but it cannot enhance the bone density, and cannot prevent the sclerotin degenerate and bone quantity loss of emasculate rats. (4) L-Arg of different dosages have different influences on the blood biochemistry of the osteoporosis rats, so we may adjust the L-Arg dosage according to the blood biochemistry value. (5) After hypodermic injection of low and middle dosage of L-Arg, there is a performance of low calcium and high phosphorus, and there is a performance of low phosphorus after hypodermic injection of high dosage. We can apply low and middle dosage of L-Arg to prevent and cure osteoporosis after menopause, but during the treatment period we should pay attention to calcium supplement.