Effect Of High Altitude On Biochemical Indexes And Expression Of TGF-β1 During The Healing Process Of Rat Radius Fracture

Objective: To demonstrate the mechanism of delayed union and nonunion during the fracture healing process in the high altitude, we investigate the changes of expression of TGF-β1(transforming growth factor-beta1) , activity of AKP(alkaline phosphatase), content of osteocalcin, calcium and phosphorus in blood during rat radius fracture healing process in the high altitude. Methods and Materials: The radius fracture rat model was established in the high altitude. The expression of TGF-β1 in callus was observed with the methods of immunohistochemistry. The serum osteocalcin level was assayed with RIA(radioimmunoassay), and the activity of AKP, the contents of calcium and phosphorus in blood of rats were detected by automatic biochemistry analyzer. Results:(1) It is demonstrated that the process of proliferation and differentiation of osteoblasts and chondrocytes, endochondral ossification or intramembranous ossification was delayed in the high altitude group compared with the plain group with the metheod of histology.(2)3 days after radius fracture, the expression of TGF-β1 was detected in cytoplasm in both high altitude group and plain group. During the fracture healing process, the number of TGF-β1 positive cells increased and reached the peak at the 3rd week, then declined to the control level at the 6th week. Compared with the plain group, the expression of TGF-β1 in the rats of high altitude group was decreased significantly, especially at the 3rd day(0.5392±0.0379 to 0.4298±0.033 P<0.01)and the 3rd week (0.7920±0.0527 to 0.6122±0.0295 P<0.01). (3) The osteocalcin level of the high altitude group increased slowly during earlyhealing period, while at the 2nd week, the osteocalcin level increased quickly and was higher than the control high altitude group (0.82±0.12 to 1.63±0.33ng/L P<0.01), but the peak was still lower than the plain group (3.23±0.16 to 1.76±0.40ng/ml P<0.01). (4)Compared with the plain group, the increase of AKP activity in the rats of high altitude was delayed and reached the peak at the 3rd week, and the peak level of AKP activity was lower (513±69 to 380±42IU/L P<0.05). (5) Compared with the plain group, the peak of calcium concentration was obviously delayed in the high altitude group,while the level of blood calcium and phosphorus has no significant difference to the plain group. However, the product of calcium and phosphorus was increased more slowly and the peak kept shorter time in the high altitude group. Conclusion:(1) The process of proliferation and differentiation of osteoblasts and chondrocytes, endochondral ossification or intramembranous ossification was delayed in the high altitude group compared with the plain group.(2)TGF-β1 plays a important role in fracture healing, especially to regulate differentiation and proliferation of cells in the high altitude region. (3) During the rat radius fracture healing process, the expression of TGF-β1, the serum osteocalcin level, the activity of AKP and the content of calcium and phosphorus in blood were lower in the high altitude group than in the plain group. (4)The decreasing biologic action of the osteocyte, osteoblast and osteoclast group has impact on fracture healing in the high altitude.