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Organ transplantation is the most effective treatment for all categories of end-stage organ diseases. To resolve the shortage of donors in organ transplantation, widespread attention has been diverted to xenotransplantation. At present, clinicians mainly highlight the problems related to xenotransplantation rejection and viral infection. The physiology of xenotransplantation has been rarely studied. Kidney performs endocrine function by producing erythropoietin (EPO), renin and activating vitamin D. Although these pathways are usually well preserved in allogeneic transplantation, species-specific differences, especially those between pigs and non-human primates, may still affect the physiological function of transplant organs. In this article, the changes of EPO, renin-angiotensin-aldosterone system (RAAS) and active vitamin D3 of pig and human after xenotransplantation were illustrated, aiming to provide reference for subclinical research of xenotransplantation.
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Objective To investigate the effects of 1,25-dihydroxy vitamin D3 [1,25 (OH)2D3] on food allergy(FA) in mice and its mechanism.Methods A total of 40 BALB/c mice were randomly divided into 5 groups,8 in each group,including control group (group C) and FA model group (FA group),according to the dose of 1,25 (OH)2 D3 intervention,the mice of the FA group were divided into FA0 group (0),FA1 group [10 μg/(kg · d)],FAm group [50 μg/(kg · d)] and FAh group[100 μg/(kg · d)].Egg albumin was used to establish a food allergy model,with different doses of 1,25 (OH)2D3 for gastric intervention,and the control group was replaced by 9 g/L saline.The serum levels of ovalbumin-immunoglobulin E(OVA-IgE),interleukin (IL)-9 and IL-17 of mice were measured by using enzyme linked immunosorbent assay after the last excitation,and HE staining and histopathological examination were carried out in the small intestine of mice.Results Compared with group C,FAo group and FAh group small intestinal mucosa in mice had different degrees of damage,partial peeling off,structure disorder,villi epithelial cell focal falls peeling off,necrosis,lamina propria edema,congestion,a large number of inflammatory cells infiltration,low but the FA1 group and FAm group had light mucosa damage,intestinal epithelial basically intact,with integrity,no congestion,edema,and inflammatory cells infiltration to a lesser degree.The mean concentrations of serum IgE,IL-9 and IL-17 in different groups were statistically significant (F =40.770,9.530,5.624,all P ＜ 0.05).Compared with the FA0 group [(41.87 ±3.19) ng/L],the OVA-IgE of the FA1 group [(22.71 ±4.77) ng/L] and the FAm group [(16.34 ±2.81) ng/L] were significantly reduced (t =5.533,1 1.835,all P ＜ 0.01),but there was no significant difference between the FAh group [(36.29 ± 6.52) ng/L] (t =1.673,P ＞ 0.05).Compared with the FA0 group [(161.77 ±50.44) ng/L],the IL-9 levels of the FA1 group [(94.29 ± 18.79) ng/L] and the FAm group [(84.45 ± 30.88) ng/L] were significantly lower (t =3.267,3.366,all P ＜ 0.01),while that of the FAh group [(36.29 ±6.52) ng/L] was not significantly lower (t =0.777,P ＞0.05).Compared with FA0 group [(81.55 ±29.37) ng/L],IL-17 levels of FAh group [(133.58 ± 47.05) ng/L] was significantly increased (t =2.653,P ＜0.05),while IL-17 level of FA1 group [(79.41 ± 25.15) ng/L] and FAm group [(58.81 ± 26.00) ng/L] were lower than that of FAo group [(81.55 ±29.37) ng/L],but the difference was not statistically significant (t =0.154,1.640,all P ＞ 0.05).Conclusions Low,medium dose of 1,25 (OH) 2 D3 supplements can inhibit mice food allergies,but high doses of 1,25 (OH)2 D3 improve performance in mice food allergies,and 1,25 (OH)2 D3's influence on the secretion of IL-9 is one that influences mechanism of food allergy.
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Objective@#To investigate the effects of 1, 25-dihydroxy vitamin D3[1, 25(OH)2D3] on food allergy(FA) in mice and its mechanism.@*Methods@#A total of 40 BALB/c mice were randomly divided into 5 groups, 8 in each group, including control group (group C) and FA model group (FA group), according to the dose of 1, 25(OH)2D3 intervention, the mice of the FA group were divided into FA0 group (0), FAl group [10 μg/(kg·d)], FAm group [50 μg/(kg·d)] and FAh group[100 μg/(kg·d)]. Egg albumin was used to establish a food allergy model, with different doses of 1, 25(OH)2D3 for gastric intervention, and the control group was replaced by 9 g/L saline.The serum levels of ovalbumin-immunoglobulin E(OVA-IgE), interleukin(IL)-9 and IL-17 of mice were measured by using enzyme linked immunosorbent assay after the last excitation, and HE staining and histopathological examination were carried out in the small intestine of mice.@*Results@#Compared with group C, FA0 group and FAh group small intestinal mucosa in mice had different degrees of damage, partial peeling off, structure disorder, villi epithelial cell focal falls peeling off, necrosis, lamina propria edema, congestion, a large number of inflammatory cells infiltration, low but the FAl group and FAm group had light mucosa damage, intestinal epithelial basically intact, with integrity, no congestion, edema, and inflammatory cells infiltration to a lesser degree.The mean concentrations of serum IgE, IL-9 and IL-17 in different groups were statistically significant (F=40.770, 9.530, 5.624, all P<0.05). Compared with the FA0 group [(41.87±3.19) ng/L], the OVA-IgE of the FAl group [(22.71±4.77) ng/L] and the FAm group [(16.34±2.81) ng/L] were significantly reduced (t=5.533, 11.835, all P<0.01), but there was no significant difference between the FAh group [(36.29±6.52) ng/L] (t=1.673, P>0.05). Compared with the FA0 group [(161.77±50.44) ng/L], the IL-9 levels of the FAl group [(94.29±18.79) ng/L] and the FAm group[(84.45±30.88) ng/L] were significantly lower (t=3.267, 3.366, all P<0.01), while that of the FAh group [(36.29±6.52) ng/L] was not significantly lower (t=0.777, P>0.05). Compared with FA0 group [(81.55±29.37) ng/L], IL-17 levels of FAh group [(133.58±47.05) ng/L] was significantly increased (t=2.653, P<0.05), while IL-17 level of FAl group [(79.41±25.15) ng/L] and FAm group [(58.81±26.00) ng/L] were lower than that of FA0 group [(81.55±29.37) ng/L], but the difference was not statistically significant (t=0.154, 1.640, all P>0.05).@*Conclusions@#Low, medium dose of 1, 25(OH)2D3 supplements can inhibit mice food allergies, but high doses of 1, 25(OH)2D3 improve performance in mice food allergies, and 1, 25(OH)2D3′s influence on the secretion of IL-9 is one that influences mechanism of food allergy.
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Objective To observe the effect of fluoride on fibroblast growth factor 23 (FGF23) in bone tissue of mice,and to explore the role of FGF23 in fluoride-induced bone injury.Methods Sixty-four Balb/c mice,half male and female,were divided into 4 groups based on body weight via the random number table method and 16 mice were in each group.The mice in control group,low fluoride group,middle fluoride group and high fluoride group were treated with 0,25,50,and 100 mg/L F-distilled water,respectively.After three months,the mice were put to death and the prevalence of dental fluorosis was calculated.The fluoride contents in spine were detected via the fluoride-ion selective electrode method,serum content of calcium and phosphorus were detected by micro enzyme labeled method.The levels of FGF23,parathyroid hormone (PTH) and 1,25 dihydroxy vitamin D3 [1,25 (OH)2D3] in serum were measured by enzyme-linked immunosorbent assay.The FGF23 protein expression levels in bone tissue were determined by immunohistochemistry and Western blotting.Results The rates of dental fluorosis in low,medium and high fluoride groups were 75％ (4/16),100％ (16/16) and 100％ (16/16),respectively.Compared with control group [0 (0/16)] the differences were statistically significant (P ＜ 0.05).The levels of fluoride in the fluoride group [low,medium,high fluoride groups:(1 730.86 ± 165.90),(2 400.58 ± 286.65),(3 980.88 ± 511.65) mg/kg] were higher than that of control group [(854.30 ± 89.05) mg/kg,P ＜ 0.05].There was no difference in serum calcium content among groups (F =0.05,P ＞ 0.05).The contents of phosphorus in the serum of the medium and the high fluoride groups [(2.46 ± 0.32),(2.48 ± 0.73) mmol/L] were lower than those in the control and the low fluoride groups [(2.89 ± 0.45),(3.25 ± 0.69) mmol/L,P ＜ 0.05].The serum PTH and 1,25 (OH)2D3 content increased first and then decreased.The expression of FGF23 in middle and high fluoride groups [(660.84 ± 64.18),(638.74 ± 121.23) ng/L] was up-regulated compared with that of control group [(613.53 ± 98.18) ng/L].The expression of FGF23 protein in cortical bone increased gradually with the dose of fluoride.Western blotting results showed that the content of FGF23 protein in the bone tissue of mice was significantly increased in the low fluoride group (1.58 ± 0.46) and the middle fluoride group (1.40 ± 0.41) compared with that of control group (1.00 ± 0.41),the differences were statistically significant (P ＜ 0.05).Conclusions The phosphorus,FGF23,PTH,and 1,25 (OH)2D3 levels in the serum and FGF23 protein levels in the bone tissue of fluorosis mice have changed.It may be suggested that FGF23 interacts with PTH and 1,25 (OH)2D3 to influence the level of calcium and phosphorus metabolism in the body and participate in the formation of skeletal fluorosis.
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Objective To discuss the effects of bacteria lysates (OM-85BV),1,25-dihydroxy vitamin D3 [1,25-(OH)2-VitD3],two immune regulators on airway inflammation in asthmatic mice models,and its pathways of action on airway inflammation were discussed.Methods Forty male BALB/c mice graded 4-6 weeks were randomly divided into 5 groups.Group A:control group;group B:asthmatic model group;group C:1,25-(OH)2-VitD3 group;group D:OM-85BV group;group E:combination group.On days 0 to 14,mice in C,D and E groups were given 1,25-(OH)2-VitD3,OM-85BV and 1,25-(OH)2-VitD3 + OM-85 BV,and mice in A,B groups were given 9 g/L saline instead.On days 15,22 and 29,mice in B,C,D,E groups were intraperitoneally with injection of ovalbumin(OVA)-aluminum hydroxide [Al(OH)3].Group A were given 9 g/L saline instead.On days 36 to 40,mice of B,C,D,E groups were given an aerosol challenge of 10 g/L OVA for 0.5 h once a day.Mice in the control group were given the same amount of 9 g/L saline.Animals were sacrificed 24 hours after the final inhalational challenge,and for the recovered bronchoalveolar lavage fluid(BALF) of the left lung was used for differential inflammatory cell counts and for detecting the level of inflammatory cytokine interleukin-17 (IL-17).Right lung samples were used for pathological investigation and detecting the expression of the IL-17 mRNA and RORγt mRNA by real time-PCR.Results Compared with the control group,the asthma models expressed more serious expression in bronchospasm contraction,hyperplasia disorders of bronchial epithelial cells,infiltration of inflammatory cells in lung,and so on.Compared with the control group,the total number of inflammatory cells counts[(104.04 ±5.51) 107/L vs (22.79 ± 1.91) 107/L] and eosinophils proportion [(37.63 ± 3.64) ％ vs (2.37 ± 1.55) ％] in BALF in group B were significantly increased (all P ＜ 0.05),the levels of IL-17 [(85.13 ± 5.77) 103 pg/L vs (47.44 ± 4.57) 103 pg/L] in BALF were significantly higher(P ＜ 0.05),the relative expressions of IL-17 mRNA (13.68 ± 1.59 vs 1.00 ± 0.00) and RORγt mRNA (4.53 ± 0.51 vs 1.00 ± 0.00) in lung were higher,which had a statistical significance (all P ＜ 0.05).The situations of group C,D,E were obviously improved compared with group B,and those of group D were improved remarkably.Conclusions Oral OM-85BV and 1,25-(OH)2-VitD3 intervention could relieve the airway inflammation of asthmatic mice models,and its effect can be remarkable by oral OM-85BV.The two immune regulators could relieve the degree of airway inflammation on asthmatic mice models by reducing the expression of Th17 cells differentiation.Therefore the two immune regulators could be the choices for preventing the happening and the development of the asthmatic airway inflammation.
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OBJECTIVE@#To investigate the essential biochemical indices like 1 -hydroxylase and hypocalcaemia in the rats with severe acute pancreatitis and explore the correlation between them.@*METHODS@#A total of 120 SPF grade Wistar male rats which were in similar physiological status were selected and randomly divided into two groups: sham group (SO group) and severe acute pancreatitis group (SAP group). Then they were divided into 1 h, 3 h, 6 h, and 12 h subgroups according to the killing time. The severe acute pancreatitis model was established by retrograde injection of 5% sodium taurocholate. Serum calcium, serum creatinine, serum urea nitrogen and serum amylase were measured at different time. Serum 1, 25 dihydroxy vitamin D3 level was determined by enzyme linked immunosorbentassay. The expression of 1-hydroxylase protein in the kidney tissue was determined with Western blotting and immunohistochemistry to observe its location. The pathologic features of the kidney tissue section was observed under light microscope and submicroscopic structure of the proximal convoluted tubule epithelial cell was observed under transmission electron microscope.@*RESULTS@#Compared with the SO group, rats in the SAP group showed continuous pathological injury as time went by. There was significant increase in serum creatinine, serum urea nitrogen and serum amylase in SAP group compared with the SO group 1, 3, 6, 12 hours after the operation (P<0.05). There was significant decrease in serum calcium and 1, 25 dihydroxy vitamin D3 3, 6, 12 hours after the operation (P<0.05). It also showed that the expression of the 1-hydroxylase protein in kidney tissues was upregulated at 1 h, 3 h and decreased at 6 h, 12 h compared with the SO group. The serum calcium, 1, 25 dihydroxy vitamin D3 and the expression of the 1-hydroxylase protein in kidney tissues of the SAP group showed sustaining decrease. Western blotting showed positive correlation between the 1-hydroxylase expression and serum calcium at 3 h, 6 h and 12 h (r=0.976, P<0.001; r=0.948, P<0.001; r=0.742, P=0.001) and also positive correlation between the 1-hydroxylase expression and serum 1, 25 dihydroxy vitamin D3 at 1 h, 3 h, 6 h and 12 h (r=0.935, P<0.001; r=0.952, P<0.001; r=0.917, P<0.001; r=0.874, P<0.001).@*CONCLUSIONS@#At the early stage of the kidney injury, the expression of 1-hydroxylase in the kidney tissue is reduced with the progress of the disease and the decrease in its activity has a correlation with the hypocalcaemia.
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Objective: To investigate the essential biochemical indices like 1 -hydroxylase and hypocalcaemia in the rats with severe acute pancreatitis and explore the correlation between them. Methods: A total of 120 SPF grade Wistar male rats which were in similar physiological status were selected and randomly divided into two groups: sham group (SO group) and severe acute pancreatitis group (SAP group). Then they were divided into 1 h, 3 h, 6 h, and 12 h subgroups according to the killing time. The severe acute pancreatitis model was established by retrograde injection of 5% sodium taurocholate. Serum calcium, serum creatinine, serum urea nitrogen and serum amylase were measured at different time. Serum 1, 25 dihydroxy vitamin D3 level was determined by enzyme linked immunosorbentassay. The expression of 1-hydroxylase protein in the kidney tissue was determined with Western blotting and immunohistochemistry to observe its location. The pathologic features of the kidney tissue section was observed under light microscope and submicroscopic structure of the proximal convoluted tubule epithelial cell was observed under transmission electron microscope. Results: Compared with the SO group, rats in the SAP group showed continuous pathological injury as time went by. There was significant increase in serum creatinine, serum urea nitrogen and serum amylase in SAP group compared with the SO group 1, 3, 6, 12 hours after the operation (P<0.05). There was significant decrease in serum calcium and 1, 25 dihydroxy vitamin D3 3, 6, 12 hours after the operation (P<0.05). It also showed that the expression of the 1-hydroxylase protein in kidney tissues was upregulated at 1 h, 3 h and decreased at 6 h, 12 h compared with the SO group. The serum calcium, 1, 25 dihydroxy vitamin D3 and the expression of the 1-hydroxylase protein in kidney tissues of the SAP group showed sustaining decrease. Western blotting showed positive correlation between the 1-hydroxylase expression and serum calcium at 3 h, 6 h and 12 h (r=0.976, P<0.001; r=0.948, P<0.001; r=0.742, P=0.001) and also positive correlation between the 1-hydroxylase expression and serum 1, 25 dihydroxy vitamin D3 at 1 h, 3 h, 6 h and 12 h (r=0.935, P<0.001; r=0.952, P<0.001; r=0.917, P<0.001; r=0.874, P<0.001). Conclusions: At the early stage of the kidney injury, the expression of 1-hydroxylase in the kidney tissue is reduced with the progress of the disease and the decrease in its activity has a correlation with the hypocalcaemia.
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Objective:To investigate the essential biochemical indices like 1α-hydroxylase and hypocalcaemia in the rats with severe acute pancreatitis and explore the correlation between them.Methods:A total of 120 SPF grade Wistar male rats which were in similar physiological status were selected and randomly divided into two groups: sham group (SO group) and severe acute pancreatitis group (SAP group). Then they were divided into 1 h, 3 h, 6 h, and 12 h subgroups according to the killing time. The severe acute pancreatitis model was established by retrograde injection of 5% sodium taurocholate. Serum calcium, serum creatinine, serum urea nitrogen and serum amylase were measured at different time. Serum 1, 25 dihydroxy vitamin D3 level was determined by enzyme linked immunosorbentassay. The expression of 1α-hydroxylase protein in the kidney tissue was determined with Western blotting and immunohistochemistry to observe its location. The pathologic features of the kidney tissue section was observed under light microscope and submicroscopic structure of the proximal convoluted tubule epithelial cell was observed under transmission electron microscope. Results:Compared with the SO group, rats in the SAP group showed continuous pathological injury as time went by. There was significant increase in serum creatinine, serum urea nitrogen and serum amylase in SAP group compared with the SO group 1, 3,6,12 hours after the operation (P<0.05). There was significant decrease in serum calcium and 1, 25 dihydroxy vitamin D3 3,6,12 hours after the operation (P<0.05). It also showed that the expression of the 1α-hydroxylase protein in kidney tissues was upregulated at 1 h, 3 h and decreased at 6 h,12 h compared with the SO group. The serum calcium, 1, 25 dihydroxy vitamin D3 and the expression of the 1α-hydroxylase protein in kidney tissues of the SAP group showed sustaining decrease. Western blotting showed positive correlation between the 1α-hydroxylase expression and serum calcium at 3 h, 6 h and 12 h (r=0.976,P<0.001;r=0.948,P<0.001; r=0.742, P=0.001) and also positive correlation between the 1α-hydroxylase expression and serum 1, 25 dihydroxy vitamin D3 at 1 h,3 h, 6 h and 12 h (r=0.935,P<0.001;r=0.952,P<0.001;r=0.917,P<0.001; r=0.874, P<0.001).Conclusions:At the early stage of the kidney injury, the expression of 1α-hydroxylase in the kidney tissue is reduced with the progress of the disease and the decrease in its activity has a correlation with the hypocalcaemia.
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PURPOSE: To find out the possible role of 1,25(OH)2 vitamin D3 [1,25(OH)2D3] and parathyroid hormone (PTH) as intrinsic factors in urinary calcium stone formers (SFs), we investigated their relationship with serum and urinary biochemical parameters. MATERIALS AND METHODS: A total of 326 calcium SFs (male: 204, female: 122) were enrolled and underwent outpatient metabolic evaluations including 1,25(OH)2D3 and PTH as well as serum and 24-hour urinary biochemical parameters. As control, 163 age- and sex-matched (2:1) individuals (non-SFs) who have never urinary stone episode were included. RESULTS: 1,25(OH)2D3 level was positively correlated with urinary calcium excretion (r=0.347, p<0.001). The hypercalciuric group and recurrent SFs had higher serum 1,25(OH)2D3 levels than the normocalciuric group (p<0.001) and first SFs (p=0.050). In the adjusted multiple linear regression analysis, serum 1,25(OH)2D3 level (beta=0.259, p<0.001) and serum PTH level (beta=-0.160, p<0.001) were significantly correlated with urinary calcium excretion. The patients in highest tertile of 1,25(OH)2D3 had a more than 3.1 fold risk of hypercalciuria than those in the lowest tertile (odds ratio=3.14, 95% confidence interval: 1.431-6.888, p=0.004). No correlation was observed between PTH and 1,25(OH)2D3 (R=0.005, p=0.929) in calcium SFs, while a negative correlation was found in controls (R=-0.269, p=0.001). CONCLUSION: 1,25(OH)2D3 was closely correlated with urinary calcium excretion, and high 1,25(OH)2D3 levels were detected in the hypercalciuric group and in recurrent SFs. However, 1,25(OH)2D3 was not correlated with PTH in calcium SFs. These findings suggest that 1,25(OH)2D3 might be important intrinsic factor for altered calcium regulation in SFs.
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Adult , Female , Humans , Male , Middle Aged , Calcium/metabolism , Kidney Calculi , Linear Models , Multivariate Analysis , Odds Ratio , Parathyroid Hormone/blood , Vitamin D/analogs & derivativesABSTRACT
Objective To investigate the renal level of 1o-hydroxylase and the change of serum calcium in rats with severe acute pancreatitis,and their correlation.Methods Eighty male Wistar rats were randomly (random number) divided into two groups:sham operation group (SO group),severe acute pancreatitis group (SAP group),and each group was further randomly divided into 1 h,3 h,6 h,and 12 h subgroups (n =10).Severe acute pancreatitis model was made by retrograde infusion with 5％ sodium taurocholate solution into the biliopancreatic duct,rats were sacrificed at 1 h,3 h,6 h,and 12 h separately after modeling.The levels of serum amylase,serum calcium,serum urea nitrogen,serum creatinine,serum 1,25-dihydroxy vitamin D3 were measured,and the level of lα-hydroxylase protein in the kidney was determined with immunohistochemistry and Western blotting.The histopathologic changes of kidney tissue were observed under light microscope and the changes of the proximal tubular epithelial cell were observed under electron microscope.Results Compared with SO group,the levels of serum amylase,serum urea nitrogen,and serum creatinine were higher in SAP group,but the levels of serum calcium and 1,25-dihydroxy vitamin D3 decreased at 3,6,and 12 h,and the renal level of 1 α-hydroxylase also decreased at 3,6,and 12 h after modeling.In SAP group,the levels of serum calcium,serum 1,25-dihydroxy vitamin D3 and the renal level of 1 α-hydroxylase gradually decreased,and the renal level of 1 α-hydroxylase and the level of serum 1,25-dihydroxy vitamin D3 had positive correlation at 3 h,6 h,and 12 h (r =0.93,P ＜0.01; r=0.951,P ＜0.01; r =0.92,P ＜0.01; r =0.878,P ＜0.01),and the renal level of 1α-hydroxylase and the level of serum calcium had positive correlation at 3 h,6 h,and 12 h (r =0.975,P ＜0.01; r=0.946,P＜0.01; r=0.747,P＜0.01).Conclusions Intheearly course of SAP,the lowered activity of 1 α-hydroxylase may play an important role in the development of hypocalcemia.
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Objective:To observe the inhibitory effects of VD3 and Tamoxifen on ER-negative breast cancer cells transfected with human recombinant pVDRE-Tk-ER? eukaryotic expression plasmid in vivo. Method:A recombinant human ER? expression plasmid containing 4 copies of VDRE and Tk promoter was introduced into the ER-negative MDA-MB-231 breast cancer cell. The transformed breast cancer cells were inoculated into athymic nude mice. 4 w after tumor inoculation,mice bearing the tumor of approximately 200 mm3 were treated with 0.5?g/kg of VD3 and/or 50mg/kg of Tamoxifen(SC) for 20d. The tumor volume was precisely measured,concurrently HE stain and Ki-67 immunohistochemical(IHC) assay were performed to detect the anti-proliferative effect of Vit D3 in combination with Tamoxifen in vivo. Results:After 20d of treatment,VD3 and Tamoxifen synergistically decreased the tumor volume as compared with control group. And the IHC results also showed that the Ki-67 expression was significantly inhibited by co-treatment of VD3 and Tamoxifen,which means the arrest of cell cycle progression. Conclusion:VD3 could effectively restore the sensitivity of ER-negative breast cancer cells to Tamoxifenby inducing the expression of exogenous ER? gene through the VDRE and Tk promoter in vivo.