| Research BasicsDiabetic retinopathy(DR)is an important microvascular complication of diabetes,and it is also the leading cause of blinding disease of working age population in our country.The mechanism of occurrence and development of DR is complex,and chronic inflammation and neovascularization play an important role in it.Sonic hedgehog(SHH)signaling pathway is an important signaling pathway that regulates embryonic development and tissue differentiation and growth.The SHH signaling pathway plays a key role in the growth and metastasis of tissue proliferative diseases such as tumors and neovascularization of lesions.The SHH signaling pathway can play a role in promoting angiogenesis by regulating the expression of angiopoietin(Ang)and vascular endothelial growth factor(VEGF).And at the same time,it can participate in chronic inflammation by affecting the expression of IL and other inflammatory factors.In the field of ophthalmology,the SHH signaling pathway is mainly involved in eyeball development and repair of tissue growth in the eye,and its abnormal activation can lead to the formation of new blood vessels.As a secreted protein,SHH protein is the initial signaling factor of this pathway.By binding to membrane proteins,it activates downstream transcription factors to act on the target gene and promotes the expression of VEGF,Ang-2 and other angiogenic factors.Low-density lipoprotein receptor-related protein 2(LRP2)is a co-receptor of the SHH signaling pathway.It can inhibit the excessive activation of the SHH signaling pathway by endocytosis of the SHH protein.Therefore,the SHH signaling pathway regulated by LRP2 has broad prospects in the study of diabetic retinopathy.ObjectiveBy detecting the expression of SHH,LRP2,Ang-2 and VEGF in the serum and vitreous of patients with diabetic retinopathy,and comparing the difference between the expression of serum and vitreous in patients with non-diabetic retinopathy,whether the SHH signaling pathway is involved in diabetic retinopathy Occurrence and development.Analyze the correlation between local factor concentrations in patients with diabetic retinopathy,speculate the effect of SHH signaling pathway in the development of diabetic retinopathy,and whether LRP2 plays a regulatory role in diabetic retinopathy.To evaluate the significance and clinical value of the SHH signaling pathway in the diagnosis and treatment of diabetic retinopathy,with a view to finding new molecular markers or therapeutic targets for the diagnosis and treatment of diabetic retinopathy.MethodsForty eyes of 40 patients with 23 G vitrectomy in the first affiliated hospital of zhengzhou university between January 2019 and December 2019 were screened,among which 20 eyes of 20 patients were treated with proliferative diabetic retinopathy in the experimental.group and 20 eyes of 20 patients with simple rhegmatogenous retinal detachment in the control group.On the morning of the operation day,2mL of venous blood was collected from all patients on an empty stomach.After centrifugation,,0.6ml of supernatant was taken and transferred to the refrigerator at-80℃.During the operation of 23G vitreous resection,the standard three channels were used,and under the condition of no perfusion,0.5ml vitreous fluid was extracted from the vitreous cavity,and 0.2ml supernatant was taken after centrifugation,which was transferred to the refrigerator at-80 ℃.The expression levels of SHH,LRP2,ang-2 and VEGF in the samples were measured by enzyme-linked immunosorbent assay.SPSS statistical software was used for statistical analysis of the data.The test standard was set as α=0.05.The measurement data is subjected to t test or non-parametric test,the qualitative data is applied to line c,and the correlation analysis is performed with Pearson test.Results1.The serum SHH concentration was 2198.69±811.10 pg/mL in the experimental group and 1484.39±507.73 pg/mL in the control group.The difference of serum SHH concentration between the two groups was statistically significant(P=0.002)and the concentration in the experimental group was higher than that in the control group.The vitreous SHH concentration was 3522,27±590.24 pg/mL in the experimental group and 3115.99±289.82 pg/mL in the control group.The difference of vitreous SHH concentration between the two groups was statistically significant(P=0.009)and the concentration in the experimental group was higher than that in the control group.2.The Serum LRP2 concentration was 1804.84±637.59 pg/mL in the experimental group and 2352.14±884.65 pg/mL in the control group.The difference in serum LRP2 concentration between the two groups was statistically significant(P=0.031),and the concentration in the experimental group was lower than that in the control group.The concentration of LRP2 in vitreous was 2699.12±160.08 pg/mL in the experimental group and 2826.78±190.33 pg/mL in the control group.The concentration of LRP2 in vitreous of the two groups was statistically significant(P=0.027),and the concentration in the experimental group was lower than that in the control group.3.The serum Ang-2 concentration was 8.37±2.04 ng/mL in the experimental group and 6.56±2.31 ng/mL in the control group.The difference of the serum Ang-2 concentration between the two groups was statistically significant(P=0.012),and the concentration of the experimental group was higher than that of the control group.The concentration of Ang-2 in vitreous was 14.42±1.31 ng/mL in the experimental group and 13.49±1.10 ng/mL in the control group.The difference of the concentration of Ang-2 in the two groups was statistically significant(P=0.020),and the concentration in the experimental group was higher than that in the control group。4.The serum VEGF concentration was 159.17±96.41 pg/mL in the experimental group and 131.38±89.78 pg/mL in the control group.There was no statistically significant difference in the serum VEGF concentration between the two groups(P>0.05).The concentration of VEGF in vitreous was 174.63±14.19 pg/mL in the experimental group and 168.16±11.45 pg/mL in the control group.There was no statistically significant difference in the concentration of vitreous VEGF between the two groups(P>0.05).5.In the vitreous of the experimental group,SHH concentration was negatively correlated with LRP2 concentration(r=-0.522,P<0.05)and positively correlated with Ang-2 concentration(r=0.475,P<0.05).Conclutions1.The expression of SHH protein is increased in the serum and vitreous of patients with diabetic retinopathy,suggesting that the Sonic hedgehog signaling pathway may be involved in the development of diabetic retinopathy.2.In patients with diabetic retinopathy,the concentration of vitreous LRP2 decreased,and the concentration of LRP2 in vitreous was negatively correlated with the concentration of SHH,suggesting that in diabetic retinopathy,LRP2 may negatively regulate the SHH signaling pathway.Decreased inhibition of SHH signaling due to decreased LRP2 concentration may be a mechanism for the development of diabetic retinopathy.3.In patients with diabetic retinopathy,the expression of Ang-2 in serum and vitreous was increased,and the expression of Ang-2 in vitreous was positively correlated with SHH,suggesting that the SHH signaling pathway may promote the development of diabetic retinopathy by regulating the expression of Ang-2. |
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