| BackgroundAccording to the latest research,by 2017,there are about 697.5 million Chronic Kidney Diseases(CKD)patients globally,accounting for 9.1%of the global population,while China has 132.3 million patients,ranking the first in the world.Abnormal mineral bone metabolism is a complication of CKD stage 2-3,presenting as abnormal metabolism of calcium and phosphorus,parathormone(PTH),fibroblast growth factor-23(FGF-23),abnormal bone transformation and mineralization,and vascular calcification.Secondary hyperparathyroidism(SHPT)is the main component,continued progression not only leads to metastatic calcification and symptoms such as lion-faced,short stature and bone pain,but also increases the risk of cardiovascular events and all-cause mortality.Parathyroidectomy(PTX)is the main clinical treatment for refractory SHPT patients.Recent studies suggest that microinflammatory states are prevalent in CKD patients.The major markers of High sensitivity c-reactive protein(hs-CRP)and Interleukin 6(IL-6)are usually increased with the progression of CKD,and is often directly or indirectly related to many complications.Existing studies have mainly analyzed the relationship between abnormal indicators of mineral bone metabolism and microinflammatory state in patients with different stages of CKD or who have entered the stage of dialysis,however,the changes of perioperative microinflammatory state in refractory SHPT patients before and after PTX surgery have not been reported.The purpose of this study was to observe the changes and correlations between perioperative mineral bone metabolism and inflammatory factors in refractory SHPT patients.Furthermore,in vitro cell experiments were conducted to further verify whether mineral bone metabolism-related indicators were involved in the regulation of inflammatory factors.ObjectiveHuman liver cells LO2(the main cell in the body that secretes the inflammatory factor CRP)were observed to secrete high sensitivity c-reactive protein(hs-CRP)under different concentrations of parathyroid hormone-related protein(PTHrP)and FGF-23,to further explore whether iPTH,FGF-23 is the factors regulating the inflammatory factor hs-CRP.Methods1.Clinic trial47 patients who underwent PTX in Henan Provincial peoples Hospital from January 2018 to August 2019 were selected as the study object,fasting venous blood was collected from the subjects preoperative(day 1 of admission)and postoperative 4 days,meanwhile,20 healthy people were collected as the control group.Clinical data of subjects were collected including:Sex,age,hemoglobin,erythropoietin(EPO),ferritin,albumin,triglyceride,total cholesterol,serum calcium,phosphorus,iPTH,etc.The following indexes were determined by enzyme linked immunosorbent assay(ELISA),including intact parathyroid hormone(iPTH),FGF-23;Bone formation marker[bone specific alkaline phosphatase(BAP),type I collagen amino-terminal propeptide(PINP);Bone absorption marker[type I collagen c-terminal peptide(CTX-I),tartrate-resistant acid phosphatase(TRAP-5b);Serum inflammatory factor[hs-CRP,IL-6].2.Cell experimentAn in vitro human liver cell(LO2)culture model was established,Mineral bone metabolism related indicators iPTH,FGF-23 stimulation LO2,collection of superfine to detect the level of inflammatory factors:different concentrations of iPTH and FGF-23 were added to the six-well culture plate for 24 hours,and the superqing was collected,then,detecte the level of the superqing inflammatory factor hs-CRP by ELISA.Results1.Baseline data of SHPT patients:the mineral bone metabolism index of PINP BAP,CTX-I,TRAP-5b was significantly higher than that of the normal control group,and the inflammatory factor hs-CRP,IL-6 was significantly higher than that of the normal control group,with statistically significant differences(P<0.05).2.Correlation analysis of baseline data of SHPT patients:(1)Correlation of iPTH,FGF-23 with general clinical data and mineral bone metabolism indexes of SHPT patients before surgery:Spearman or Pearson correlation analysis showed that preoperative serum iPTH was positively correlated with BAP,PINP,CTX-I,FGF-23,while iPTH was not correlated with TRAP-5b.Preoperative serum BAP and TRAP-5b PINP were positively correlated with CTX-I.(2)The correlation between iPTH,FGF-23 and inflammatory factors in SHPT patients before surgery:Spearman or Pearson correlation analysis showed that iPTH was positively correlated with hs-CRP,IL-6 before surgery.FGF-23 was positively correlated with hs-CRP,IL-6 before surgery.3.Perioperative results:(1)Changes in related indicators of mineral bone metabolism during perioperative period:serum calcium and phosphorus iPTH,FGF-23 TRAP-5b,CTX-I decreased after PTX compared with that before PTX,and the difference was statistically significant(P<0.05),BAP was higher than that before surgery,and the difference was statistically significant(P<0.05),PINP was increased compared with that before surgery,but the difference was not statistically significant(P>0.05)Changes of inflammatory markers in the perioperative period:the level of hs-CRP,IL-6 after surgery was significantly lower than that before surgery,which was statistically significant(P<0.05).4.Cell experiment results:With the increase of the concentration of LO2 cells stimulated by PTHrP,the level of hs-CRP in the superserum decreased first and then increased.FGF-23 stimulated LO2 cells,and the change of hs-CRP level in superserum showed no obvious trend.Conclusions1.iPTH involved in bone metabolism of bone formation and bone resorption,SHPT patients with preoperative osteoblast and osteoclast activity synchronous rise.2.PTX can obviously improve bone resorption.3.PTX can improve the body inflammation in patients with SHPT status.4.in vitro experiments show that PTHrP level too high or too low both cause inflammation leels,suggest there may be the most suitable PTHrP concentration range,the lowest levels of inflammation. |
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