The Effect Of ¹³¹I On Apoptosis Of Thyrocytes In Patients With Graves Disease

Objective: To investigate the changes of the apoptotic protein Fas,FasL and the anti-apoptotic protein Bcl-2 of thyrocytes in the patients with Graves disease after ¹³¹I therapy after 2 weeks and 4 weeks respectively, and compare the changes between the 2 groups(G2w and G4w);analyze the relativities between the unit dose of ¹³¹I and the apoptosis-related proteins mentioned above in the two groups;analyze the relativity between hypothyroidism after therapy and the apoptosis-related proteins.Method: 47 patients with Graves disease were divided into 2 groups randomly (G2w and G4w).22 patients were in G2w (M13, F9,19～51years,mean age 35.20±8.67,),the received dose of ¹³¹I was 564.99±370.00MBq (151.70～1554.00MBq) and the unit dose of ¹³¹I was 4.81±1.11MBq (3.33～6.91MBq).25 patients were in G4w (M10, F15, 19～62years,mean age 36.48±11.41), the received dose of ¹³¹I was 504.83±249.58 MBq (233.10～1184.00 MBq) and the unit dose of ¹³¹I was 4.99±1.26MBq (3.10～7.74 MBq). Thyroid tissue was obtained from the 47 patients by histological biopsy before ¹³¹I therapy and after ¹³¹I therapy 2 weeks or 4 weeks,and the biopsy samples were examined by immunohistochemical method for the expression of Fas,FasL and Bcl-2, using specific antibodies.Quantitative analysis was performed by MI2000 pathological image system.Compare the apoptosis-related proteins before and after therpy in each group, compare the changes between the 2 groups and analyze the relativities between the unit dose of ¹³¹I and the apoptosis-related proteins.Then we followed up the 47 patients 3 months after ¹³¹I therapy,detected the serum FT3,FT4 and sTSH concentration by RIA and analyze the relativity between sTSH and the apoptosis-related proteins.Result:1. The positive staining was brown granulations in thyrocytes.The positive staining of Fas,FasL and Bcl-2 were detected in Graves disease patients before and after therapy.2. G2w:Fas pre-therapeutic and post-therapeutic PU were 16.20±6.75, 22.84±9.31,P< 0.01; FasL pre-therapeutic and post-therapeutic PU were 14.56±4.06, 21.13±6.29,P<0.01; Bcl-2 pre-therapeutic and post-therapeutic PU were 15.22±5.94, 21.69±7.83,P<0.01.G4w: Fas pre-therapeutic and post-therapeutic PU were 15.83±5.03,21.69±4.52,P<0.01; FasL pre-therapeutic and post-therapeutic PU were 14.02±4.98,19.11±3.75,P<0.01; Bcl-2 pre-therapeutic and post-therapeutic PU were 16.63±4.73,19.06±3.44, P<0.05. The contrast of G2w and G4w: Fas P>0.05; FasL P>0.05; Bcl-2 P>0.05, there were not statistical differences between them.The standard deviations of above indexes in G4w were lower, demonstrating the variations were less.3. In the G2w,a statistically significant correlation was found between the unit dose of ¹³¹I therpy and the PU value of apoptotic protein Fas,FasL (rFas=0.631,P<0.01;rFasL=0.784,P<0.01), in contrast, for anti-apoptotic protein Bcl-2, there was no statistically correlation (rBcl-2=-0.094,P>0.05).In the G4w, a statistically significant correlation was found between the unit dose of ¹³¹I therpy and the PU value of apoptotic protein Fas,FasL (rFas=0.727,P<0.01;rFasL=0.763,P<0.01), in contrast, for anti-apoptotic protein Bcl-2, there was no statistically correlation (rBcl-2=0.102,P>0.05),which was consistent with those in the G2w.4. A significant corrlation was found between sTSH value in all the Graves disease patients and apoptosis-related proteins, rFas=0.433,P<0.05;rFasL=0.601,P<0.01;rBcl-2= -0.397,P<0.05.Conclusion:1. ¹³¹I can induce thyrocytes to express the apoptotic protein Fas,FasL and the anti-apoptotic protein Bcl-2 in patients with Graves disease.Whereas, the apoptotic protein Fas,FasL play a more important role in this process,which promote thyrocytes'apoptosis.2. The 4th week after ¹³¹I therpy is fit to be the time at which thyrocytes'apoptosis is studied.3. There is a statistically significant corrlation between the unit dose of ¹³¹I and the PU value of apoptotic protein Fas, FasL.4. It may be due to increased expression of Fas and FasL in thyrocytes of hypothyroid after ¹³¹I therpy.On the other hand,it may be owing to the over expression of Bcl-2 in thyrocytes of non-hypothyroid after ¹³¹I therpy.