Diabetic retinopathy(Diabeticretinopathy,DR)is a clinical complication characterized by progressive retinal vascular damage,inflammation and angiogenesis caused by a long-term high glucose environment in patients with diabetes.Epidemiological investigation shows that inflammation and microangiopathy mainly play a role in its pathogenesis.The Nuclearfactor--κ B(NF-κ B)pathway can affect the regulation of inflammation.Guizhou Dendrobium nobile(Dendrobiumnobile Lindl.,DNL)is a rare traditional Chinese medicine listed in the previous editions of Chinese Pharmacopoeia.Studies have shown that many components of Dendrobium nobile can reduce the expression of inflammatory factors,but it is rarely reported whether taking dried Dendrobium nobile powder has a positive effect on diabetic retinopathy,so this study will study it from two aspects of animal experiment and clinical research.Part one: a group of animal models of diabetic retinopathy were established in male SD rats.After intragastric administration of Dendrobium nobile,the glycemic index and body weight were measured.At the same time,the expressions of inflammatory factors such as Tumornecrosisfactor-α,TNF-α and vascular endothelial growth factor(Vascularendothelialgrowthfactor,VEGF)were further detected to determine whether it may reduce ocular inflammation.At the same time,the expression of related proteins and genes such as Interleukin-1 β(IL-1 β)and Caspase-1 on NF-κ B / NLRP3 pathway were detected directly;The second part: through the clinical search for patients with early diabetic retinopathy(less than or equal to stage 3),some patients were randomly given dried Dendrobium nobile powder to detect the content of inflammatory factors in blood and clinical ophthalmic imaging examination to determine whether dried Dendrobium nobile powder can effectively inhibit the process of retinal inflammation and explore whether NF-κ B/NLRP3 signal pathway can play a role in it.Part Ⅰ Effect of Dendrobium nobile dry powder on macular structure and function in patients with early diabetic retinopathyObjective: To investigate whether oral administration of Dendrobium nobile dry powder can improve visual function and macular microcirculation in patients with early diabetic retinopathy.Methods: Patients with early diabetic retinopathy diagnosed in the Department of Ophthalmology and Endocrinology of the affiliated Hospital of Zunyi Medical University were randomly divided into two groups: the experimental group(15 cases,30 eyes,twice a day)and the control group(15 cases,30 eyes).Random blood glucose,glycosylated hemoglobin(Hb A1C),liver function,renal function and islet function hormone changes were measured every month.The contents of IL-1 β and VEGF in blood were detected by ELISA.The changes of best corrected visual acuity(BCVA),intraocular pressure(IOP),choroidal thickness in OCT,FAZ area,perimeter and morphological index in OCTA,retinal microvessels in FFA and visual function in mf ERG were observed.Results: There was no significant change in BCVA and intraocular pressure in the experimental group compared with 2 months ago,the choroidal thickness in the EDI-OCT mode of OCT increased,the FAZ area,perimeter and morphological index of the experimental group decreased,and the central peak height of mf ERG increased,IL-1 β decreased and VEGF decreased in ELISA results of the experimental group(p < 0.05).The results of ELISA showed that the choroidal thickness of the experimental group was thicker than that of the experimental group(p < 0 05),and the morphological index was close to 1 in the experimental group(p < 0 05).In the control group,there were no significant changes in BCVA and IOP,choroidal thinning in OCT,larger FAZ area,larger perimeter and smaller morphological index in OCTA,and no significant change in central peak of mf ERG.Conclusion: Taking Dendrobium nobile dry powder can improve visual function,macular microcirculation and choroidal thickness in patients with early diabetic retinopathy.Part Ⅱ Inhibitory effect of Dendrobium nobile dry powder on inflammation in rat model of diabetic retinopathyObjective: To investigate the inhibitory effect of Dendrobium candidum powder on inflammation and NF-κ B/NLRP3 signal pathway in diabetic retinopathy rat model.Methods: After 75 male Sprague-Dawley rats were fed with high-fat and high-sugar diet for 4 weeks,the rat model of type 2 diabetes was established by intraperitoneal injection of streptozotocin(STZ)35mg/kg,and then FFA was performed to observe the fundus changes after 4 weeks of normal diet.They were randomly divided into 5 groups: control group(CMC-Na),model group(CMC-Na),low dose group(50mg/kg),middle dose group(100mg/kg)and high dose group(200mg/kg),with 15 rats in each group.Five rats in each group were killed randomly after 4 weeks,8weeks and 12 weeks.The expression of inflammatory cytokines VEGF,TNF-α,NF-κ B and NLRP3 m RNA in retinal tissue was detected by RT-PCR,and the expression of VEGF,TNF-α and NF-κ B / NLRP3 pathway related proteins in retinal tissue was detected by western blotting.Results: Diabetic rats with stable blood glucose and greater than or equal to16.7mmol/L could be obtained by continuous feeding with high-fat and high-sugar diet for 4 weeks and intraperitoneal injection of low-dose STZ.After 4 weeks of normal diet,diabetic retinopathy model rats with early glucose reticular changes in fundus could be found.Compared with the control group,the blood glucose increased and the body weight decreased in the diabetic model group.The expression of VEGF,TNF α,NF-κ B and NLRP3 m RNA in the model group increased,and the expression of Caspase-1,VEGF,NLRP3,TNF-α,IL-1 β and p NF-κ Bp65 protein increased,but the expression of NF-κ Bp65 protein had no significant difference.Compared with the model group,the expression of VEGF,TNF-α,NF-kappa B and NLRP3 m RNA in each dose group of Dendrobium nobile decreased significantly,and the protein expression of VEGF,TNF-α,p NF-kappa Bp65,NLRP3,Caspase-1 and IL-1 β decreased significantly at high dose and 12 weeks,but the expression of NF-kappa Bp65 protein had no significant difference.Conclusion: Dendrobium nobile dry powder inhibits the progression of inflammation in early diabetic retinopathy model rats.The best treatment dose is 200mg/kg and the best treatment time is 12 weeks.Dendrobium nobile can inhibit NF-κ B/NLRP3 signal pathway in rat retina. |