| The damage of bone in endemic fluorosis, namely skeletal fluorosis, is the main reason that caused pepole maimed,paralytic and lower their work capacity in endemic area. This disease has serious health hazards to Chinese people. The malnutrition of calcium could aggravate the toxicity of fluorid to bone, whereas calcium nutrition level has a decisive influence on the pathogenesis of endemic fluorosis. Hyper-parathyroidism is always found in skeletal fluorosis, and skeletal fluorosis could also increased externalization of PTH. PTH has an ability to transport calcium from blood to soft tissue.The acceleration of bone conversion is a significance character in skeletal fluorosis, just like many other pathological phenomenons. The target cell of fluorid is osteoblast(OB). The hyperplasia, hypertrophy and functional active of OB in endemic fluorosis lesions are earlier occurred conditions, and they play a leading role. Among the products of osteoblasts, alkaline phosphatase (ALP) has been a sign of bone formation and transformation. Osteocalcin protein (OCN), osteopontin (OPN) are also used in reflecting tacceleration of bone conversion and bone metabolism.Fluorid can stimulate the OBs being proliferation and differentiation, then, osteoblasts generate ROS, and the ROS become one of the important in endemic fluorosis oxidatie stress. The activities of Glutathione peroxidase (GPX), super oxide dismutase (SOD), and uric acid level can reflect the anti-oxidization degree. The amount of Malondialdehyde (MDA) can reflect the the quantity of ROS.In order to observe how the bone and the level of xidative stress change in different calcium nutritional status fluorosis in rats. This study established two groups of rats, one is fed with conventional bait, while the other is fed with low calcium diet, furthermore we separated each one of the two groups into two teams with different kind of water. One was bred with fluorid water, while the other was bred with conventional water as control. In other words, we had obtained control team (Group 1), fluoride team (Group 2), low calcium team (Group 3) and fluoride&low calcium team (Group 4). We used biochemical means to detect the concentration of blood calcium,the activities of SOD, GPX, ALP and the contents of MDA, uric acid and PTH in different period and different teams of rats. At the end of this study, we also observed the changes of rats' backbone from pathological ways and determined the gene expression level of PTHrP, OPN, OCN from rats' bone tissue.From the rats's backbone demineralizational pathological sections, we observed that new bone formation and immature woven bone significantly increased in Group 1, and in Group 3, we found that OBs of rats' backbone outer membrane bone was at a hyperplasy state, they were more functional active. in Group 4,cortical bone, such as moth-eaten-like, and compact bone were cancellous, a typical osteoporosis was also observed.At the end of the first week, the concentration of blood calcium in Group 2 increased,but markedly decreased in Group 4. The quantity of blood calcium in Group 2-4 constantly reduced as time going. Remarkable decreased amounts of blood calcium in Group 3 and Group 4 were observed at the end of the third month.ALP activity in Group 2 was a little higher than that of Group 1, which was still no statistic meaning. In Group 3, ALP activity was attenuated, compared with that ALP activity was strengthen from first to third month.The change of PTH and PTHrP could reflect the variation of blood calcium, they could also promote the maturation of bone. The quantity of PTH in Group 2 was incessantly increasing, and achieved a statistical significance level compared to the control group in the 2 second month. In the meaning time, same phenomenon was observed as time going. Comparatively speaking, the PTH level was greatly enhanced by two factors and was time-depending. In summary, fluoride-added and low calcium–breeding had greatly increased the PTH level from serum, while the expression level of PTHrP mRNA had also clearly enhanced in group 3 and 4, which was identical to the change of PTH. MDA was selected as a marker of the body levels of lipid peroxidation in this experiment. The level of MDA from the rats Group 2, was significantly higher than the control group after the first week. While the levels of MDA of the rats Group 3 and Group 4 were significantly higher than the control group after 1 month. The levels of MDA of the all the treated rats especially Group 4 were significantly higher than the control group for 3 month. In general we can see that the short-term drinking water for fluoride can stimulate the emergence of rats to enhance lipid peroxidation; the level of rats` lipid peroxidation increased significantly with the time of fluoride&low calcium giving. Antioxidant enzymes in the sera were in a variety of different dynamic changes.The activity of GPX in the fluoride-added and sufficient calcium-nutrition group were higher than their control group and significantly increased in 12th months. In the contrary, Activity of GPX in calcium-lack group was significantly lower than the corresponding control group in 2-8weeks; the rats in the case of nutritional deficiencies of calcium and fluoride by drinking water, their activities of GPX enzyme was greatly increased contrast to the low calcium control group for 1-4 weeks, the activity of enzyme was lower than the control group but higher than the low calcium group in the second month, and decreased to the lowest in the four groups in the fourth month.As an important antioxidant enzyme, SOD did not show significant activity change in this study. The activity of SOD was significantly increased in the low calcium- fluoride added group compare to that of control group in I week. However, inverted results were determined in the low calcium group and low calcium- fluoride added group at the end of the second month.The concentration of uric acid in the sera was selected as the marker of the level of anti-oxidation in this experiment. The concentration of uric acid was significantly increased in group 2. With the extension of time for fluoride, the concentration was from high to low. The concentration of uric acid was not significantly different from group 3 to cgroup1. The uric acid levels were from high to low in the low calcium- fluoride added group with time extended. The uric acid levels were reduced in the later experiments.These results suggest that:1. The concentration of calcium in the sera is lower than normal. The reduced calcium level in the sera of subchronic fluorosis could increase the toxicity of fluoride.2. Low calcium nutrition of excessive fluoride significantly enhance the activity of ALP increased stimulation. The increase of ALP activity indirectly reflects improvement of osteoblast activity, osteoblasts were functional active.3. Low calcium nutrition synergy effected with excessive fluoride markedly improved the level of PTH in sera and the expression of PTHrP in bone tissue, further indicated that the level of the body calcium and skeletal fluorosis is closely related lesion.4. Uric acid played an important role in the oxidative stress caused by compensatory subchronic fluorosis, and the state of oxidative stress played a certain role in skeletal fluorosis mechanism of bone lesions.
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