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Study On The Expression Of Chemokine IP10 In AITD Kidney And The Effect Of Pioglitazone Hydrochloride On It

Posted on:2021-03-17Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z F LuFull Text:PDF
GTID:1484306134454684Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Objective: Autoimmune thyroid disease(AITD)is one of the most common autoimmune diseases.It not only causes inflammatory cell infiltration of thyroid tissue and abnormal thyroid function,but also involves multiple tissues and organs outside the thyroid.Kidney disease is common in AITD,which often causes increased urine protein.In severe cases,it will lead to increased serum creatinine and increased urea nitrogen.It is called autoimmune thyroid disease-related nephropathy.However,due to the hidden disease,the kidney damage in AITD is often overlooked,and there are few studies on the mechanism and treatment of kidney damage in AITD.This topic focused on the study of the inflammatory factor of AITD kidney injury,explored the expression of chemokine IP10 in kidney with AITD,and whether the application of pioglitazone hydrochloride can effectively inhibit its expression,with a view to providing research ideas for the mechanism and treatment of AITD kidney injury.Method:1.Clinical case study: we collected the cases of patients who had undergone renal puncture in the Department of Nephrology,and divided them into AITD group and non-AITD group according to whether they are combined with AITD.The thyroid function,thyroid antibody,renal function,albumin,24-hour urinary protein and serum complement C3,complement C4,Ig A,Ig M and Ig G were compared between AITD group and non-AITD group by serological test,to observe the effect of AITD on thyroid function and renal function,and to observe the effect of AITD on immune system.Immunohistochemical staining was used to stain the kidney puncture tissue,and the staining for chemokine IP10 and TPO in the renal tissues of the two groups were observed and compared.2.Animal experiment research: Using a heterologous protein-porcine thyroglobulin dissolved in complete Freund's adjuvant,formulated as a 2mg / m L solution,to immunize 6-week-old C57 BL / 6 mice with multi-point subcutaneous injections,immunization was strengthened at 2 weeks,3 weeks,4 weeks,5 weeks,and 6 weeks.The mice in the control group were injected with saline-complete Freund's adjuvant at the same site.After 6 weeks,the mice successfully modeled were randomly divided into simple AITD group(group M)and pioglitazone hydrochloride group(group P),at the same time,a blank control group(group N)was set,with 10 animals in each group.Implementation of the intervention plan: mice in group P were given 0.2 ml of 2.0 mg / ml PIO and sodium carboxymethyl cellulose solution per day,and mice in groups N and M were given 0.2 ml of 5% sodium carboxymethyl cellulose solution per day.They were executed 4 weeks after the intervention.Indirect enzyme-linked immunosorbent assay(ELISA method),picric acid method,urease method and other methods were used to determine the plasma thyroid function,thyroid antibody,creatinine,and urea nitrogen levels of mice in each group,and to observe whether there are differences in serological indexes among mice in each group.Immunohistochemical staining and Western blot were used to observe the expression of TNF-? and IP10 in the kidney tissues of mice in each group,and to evaluate the inhibitory effect of pioglitazone hydrochloride on the kidney inflammation in mice.Result:1.Compared with the patients in the non-AITD group,the 24-hour urine protein content of the AITD group was significantly increased(P <0.05),and other renal function indicators were not significantly different between the two groups(P>0.05);2.Compared with patients in the non-AITD group,the level of serum complement C4 in the AITD group was reduced(P <0.05),and serum Ig A,Ig M,and Ig G were significantly increased(P <0.05);3.Compared with patients in non-AITD group,the positive rate of TPO immunohistochemical staining in kidney puncture tissue of AITD group was significantly increased(P <0.05);4.Compared with patients in non-AITD group,the positive rate of IP10 immunohistochemical staining in kidney puncture tissue of AITD group was significantly increased(P <0.05);5.Immunohistochemical staining for IP10 and TNF-? and Western blot proteinexpression in kidney of mice were detected.Compared with group N,the expression of IP10 and TNF-? in group M and group P was significantly higher,and that in group P was significantly lower than that in group M.Conclusion:1.TPO stained positively in kidney puncture tissues of AITD patients,which provided conditions for kidney tissues to be immune attacked by immune complexes.2.The positive staining rate of chemokine IP10 in the renal puncture tissue of the AITD group was significantly higher than that of the non-AITD group,indicating that the inflammation of the kidney tissue in the AITD patients was increased.3.Pioglitazone hydrochloride can effectively inhibit the expression of chemokine IP10 and inflammatory factor TNF-? in the kidneys of AITD mice.
Keywords/Search Tags:Autoimmune thyroid disease, Interferon induced protein 10, Pioglitazone hydrochloride, Thyroid peroxidase
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