The protective effect of Zhicao Tea Mixture on Müller cells and the expression of inflammatory factors in mice with diabetic retinopathy_Chinese Journal of Ocular Fundus Diseases

Authors：

Zhu Manhui , Tu Yuanyuan , Wang Zhenzhen , Du Jingxia , Guo Yang , Xu Jiaowen ,  Song E

Lixiang Eye Hospital of Soochow University, Suzhou 215021, China;

Corresponding?author：

Song E, Email: songe@suda.edu.cn

Keywords：

Diabetic retinopathy/physiopathology; Inflammation; Müller cells; Zhicao Tea Mixture

DOI：

10.3760/cma.j.cn511434-20191203-00397

Video：

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Objective To observe the protective effect of Zhicao Tea Mixture on Müller cells and the expression of inflammatory factors in mice with diabetic retinopathy.Methods Seventy-five C57BL/6J mice were randomly divided into the normal control group, diabetes mellitus (DM) group, low concentrations group, medium concentrations group and high concentrations group, with 16 mice in each group. The diabetes model of mice in all groups except the normal control group were established by intraperitoneal injection of STZ (60 mg/kg). Four weeks after the successful modeling, the Zhicao Tea Mixture with low (30 ml/kg), medium (60 ml/kg) and high concentrations (120 ml/kg) were respectively administered by gavage. Weight and blood glucose of mice in each group were measured every two weeks. After 8 weeks, Western blot method was used to detect the mice retina Müller cells activation marker gelatinous fibrous acidic protein (GFAP). Immunofluorescence was performed to detect the expression GFAP and glutamine synthetase (GS). Real-time quantitative PCR (RT-qPCR) and ELISA were used to determine the mRNA and protein expression levels of mouse retinal VEGF, TNF-α, IL-1β and IL-6 respectively.Results The weight of mice in the DM group was lower than that of the normal control group, and the blood glucose was increased. Zhicao Tea Mixture had no effect on the weight of DM mice, but had a significant hypoglycemic effect. The GFAP expression (t=38.318, P＜0.001) in the retina of mice in the DM group was increased and GS expression (t=29.737, P＜0.001) was decreased compared with the control group. The GFAP expression (t=13.677, 19.387, 16.305; P＜0.05) in the retina of mice in the low, medium and high concentrations group were decreased and GS expression (t=5.170, 19.399, 6.705; P＜0.05) were increased compared with the DM group. The expressions of retinal inflammatory factors VEGF, TNF-α, IL-1β and IL-6 in DM group all increased, while the expressions of the above-mentioned inflammatory factors in the retina of mice decreased in the low, medium and high concentrations group.Conclusion Zhicao Tea Mixture can decrease the blood glucose of DM mice and reduces the diabetic retinal inflammatory response.

Citation： Zhu Manhui, Tu Yuanyuan, Wang Zhenzhen, Du Jingxia, Guo Yang, Xu Jiaowen, Song E. The protective effect of Zhicao Tea Mixture on Müller cells and the expression of inflammatory factors in mice with diabetic retinopathy. Chinese Journal of Ocular Fundus Diseases, 2020, 36(4): 302-307. doi: 10.3760/cma.j.cn511434-20191203-00397 Copy

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10.	李晶艷, 周琦, 呂紅彬. 糖尿病早期視網膜神經元退行性病變最新研究進展[J]. 眼科新進展, 2015, 35(5): 99-102. DOI: 10.13389/j.cnki.rao.2015.0135.Li JY, Zhou Q, Lv HB. Research progress on early diabetic retinal neurodegeneration[J]. Rec Adv Ophthalmol, 2015, 35(5): 99-102. DOI: 10.13389/j.cnki.rao.2015.0135.
11.	Roy S, Kern TS, Song B, et al. Mechanistic insights into pathological changes in the diabetic retina: implications for targeting diabetic retinopathy[J]. Am J Pathol, 2017, 187(1): 9-19. DOI: 10.1016/j.ajpath.2016.08.022.
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13.	Mizutani M, Gerhardinger C, Lorenzi M. Müller cell changes in human diabetic retinopathy[J]. Diabetes, 1998, 47(3): 445-449. DOI: 10.2337/diabetes.47.3.445.
14.	Wang J, Xu X, Elliott MH, et al. Müller cell-derived VEGF is essential for diabetes-induced retinal inflammation and vascular leakage[J]. Diabetes, 2010, 59(9): 2297-2305. DOI: 10.2337/db09-1420.
15.	Shelton MD, Distler AM, Kern TS, et al. Glutaredoxin regulates autocrine and paracrine proinflammatory responses in retinal glial (Müller) cells[J]. J Biol Chem, 2009, 284(8): 4760-4766. DOI: 10.1074/jbc.M805464200.
16.	袁紅霞, 張莉芹, 馬瑾, 等. 水蛭藥用成分及主要藥理功效研究進展[J]. 甘肅醫藥, 2013, 32(4): 270-273. DOI: 10.3969/j.issn.1004-2725.2013.04.014.Yuan HX, Zhang LQ, Ma J, et al. Research progress on medicinal ingredients and main pharmacological effects of leech[J]. Gansu Medical Journal, 2013, 32(4): 270-273. DOI: 10.3969/j.issn.1004-2725.2013.04.014.
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18.	Laping NJ, Teter B, Nichols NR, et al. Glial fibrillary acidic protein: regulation by hormones, cytokines, and growth factors[J]. Brain Pathol, 1994, 4(3): 259-275. DOI: 10.1111/j.1750-3639.1994.tb00841.x.
19.	Kim Y, Truettner J, Zhao W, et al. The influence of delayed postischemic hyperthermia following transient focal ischemia: alterations of gene expression[J]. J Neurol Sci, 1998, 159(1): 1-10. DOI: 10.1016/s0022-510x(98)00146-4.
20.	Newman EA. A purinergic dialogue between glia and neurons in the retina[J]. Novartis Found Symp, 2006, 276: 193-281.
21.	Xie B, Jiao Q, Cheng Y, et al. Effect of pigment epithelium-derived factor on glutamate uptake in retinal Muller cells under high-glucose conditions[J]. Invest Ophthalmol Vis Sci, 2012, 53(2): 1023-1032. DOI: 10.1167/iovs.11-8695.

1. Zhong Y, Li J, Chen Y, et al. Activation of endoplasmic reticulum stress by hyperglycemia is essential for Müller cell-derived inflammatory cytokine production in diabetes[J]. Diabetes, 2012, 61(2): 492-504. DOI: 10.2337/db11-0315.
2. Tang J, Kern TS. Inflammation in diabetic retinopathy[J]. Prog Retin Eye Res, 2011, 30(5): 343-358. DOI: 10.1016/j.preteyeres.2011.05.002.
3. Bringmann A, Pannicke T, Grosche J, et al. Müller cells in the healthy and diseased retina[J]. Prog Retin Eye Res, 2006, 25(4): 397-424. DOI: 10.1016/j.preteyeres.2006.05.003.
4. Krishnan G, Chatterjee N. Endocannabinoids alleviate proinflammatory conditions by modulating innate immune response in muller glia during inflammation[J]. Glia, 2012, 60(11): 1629-1645. DOI: 10.1002/glia.22380.
5. Bai Y, Ma JX, Guo J, et al. Müller cell-derived VEGF is a significant contributor to retinal neovascularization[J]. J Pathol, 2009, 219(4): 446-454. DOI: 10.1002/path.2611.
6. Schmidt-Erfurth U, Garcia-Arumi J, Bandello F, et al. Guidelines for the management of diabetic macular edema by the European Society of Retina Specialists (EURETINA)[J]. Ophthalmologica, 2017, 237(4): 185-222. DOI: 10.1159/000458539.
7. 李趙偉, 梁匯珉, 李錚, 等. 羅格列酮對糖尿病視網膜Müller細胞的保護作用以及對Müller細胞膠質纖維酸性蛋白(GFAP)及炎癥因子表達的影響[J]. 眼科新進展, 2018, 38(9): 825-828. DOI: 10.13389/j.cnki.rao.2018.0195.Li ZW, Liang HM, Li Z, et al. The protective effect of rosiglitazone on diabetic retinal Müller cells and its effects on the expression of glial fibrillary acidic protein (GFAP) and inflammatory factors in Müller cells[J]. Rec Adv Ophthalmol, 2018, 38(9): 825-828. DOI: 10.13389/j.cnki.rao.2018.0195.
8. Cheng Y, Yu X, Zhang J, et al. Pancreatic kallikrein protects against diabetic retinopathy in KK Cg-A/J and high-fat diet/streptozotocin-induced mouse models of type 2 diabetes[J]. Diabetologia, 2019, 62(6): 1074-1086. DOI: 10.1007/s00125-019-4838-9.
9. Rubsam A, Parikh S, Fort PE. Role of inflammation in diabetic retinopathy[J]. Int J Mol Sci, 2018, 19(4): 942. DOI: 10.3390/ijms19040942.
10. 李晶艷, 周琦, 呂紅彬. 糖尿病早期視網膜神經元退行性病變最新研究進展[J]. 眼科新進展, 2015, 35(5): 99-102. DOI: 10.13389/j.cnki.rao.2015.0135.Li JY, Zhou Q, Lv HB. Research progress on early diabetic retinal neurodegeneration[J]. Rec Adv Ophthalmol, 2015, 35(5): 99-102. DOI: 10.13389/j.cnki.rao.2015.0135.
11. Roy S, Kern TS, Song B, et al. Mechanistic insights into pathological changes in the diabetic retina: implications for targeting diabetic retinopathy[J]. Am J Pathol, 2017, 187(1): 9-19. DOI: 10.1016/j.ajpath.2016.08.022.
12. Mello Filho P, Andrade G, Maia A, et al. Effectiveness and safety of intravitreal dexamethasone implant (Ozurdex) in patients with diabetic macular edema: a real-world experience[J]. Ophthalmologica, 2019, 241(1): 9-16. DOI: 10.1159/000492132.
13. Mizutani M, Gerhardinger C, Lorenzi M. Müller cell changes in human diabetic retinopathy[J]. Diabetes, 1998, 47(3): 445-449. DOI: 10.2337/diabetes.47.3.445.
14. Wang J, Xu X, Elliott MH, et al. Müller cell-derived VEGF is essential for diabetes-induced retinal inflammation and vascular leakage[J]. Diabetes, 2010, 59(9): 2297-2305. DOI: 10.2337/db09-1420.
15. Shelton MD, Distler AM, Kern TS, et al. Glutaredoxin regulates autocrine and paracrine proinflammatory responses in retinal glial (Müller) cells[J]. J Biol Chem, 2009, 284(8): 4760-4766. DOI: 10.1074/jbc.M805464200.
16. 袁紅霞, 張莉芹, 馬瑾, 等. 水蛭藥用成分及主要藥理功效研究進展[J]. 甘肅醫藥, 2013, 32(4): 270-273. DOI: 10.3969/j.issn.1004-2725.2013.04.014.Yuan HX, Zhang LQ, Ma J, et al. Research progress on medicinal ingredients and main pharmacological effects of leech[J]. Gansu Medical Journal, 2013, 32(4): 270-273. DOI: 10.3969/j.issn.1004-2725.2013.04.014.
17. 張博, 王曉敏, 任青華, 等. 復方水蛭素對小鼠移植瘤組織中p53、Ki-67及VEGF表達的影響[J]. 山東醫藥, 2008, 48(43): 29-30. DOI: 10.3969/j.issn.1002-266X.2008.43.014.Zhang B, Wang XM, Ren QH, et al. Effects of compound hirudin on the expression of p53, Ki-67 and VEGF in mice xenograft[J]. Shandong Medical Journal, 2008, 48(43): 29-30. DOI: 10.3969/j.issn.1002-266X.2008.43.014.
18. Laping NJ, Teter B, Nichols NR, et al. Glial fibrillary acidic protein: regulation by hormones, cytokines, and growth factors[J]. Brain Pathol, 1994, 4(3): 259-275. DOI: 10.1111/j.1750-3639.1994.tb00841.x.
19. Kim Y, Truettner J, Zhao W, et al. The influence of delayed postischemic hyperthermia following transient focal ischemia: alterations of gene expression[J]. J Neurol Sci, 1998, 159(1): 1-10. DOI: 10.1016/s0022-510x(98)00146-4.
20. Newman EA. A purinergic dialogue between glia and neurons in the retina[J]. Novartis Found Symp, 2006, 276: 193-281.
21. Xie B, Jiao Q, Cheng Y, et al. Effect of pigment epithelium-derived factor on glutamate uptake in retinal Muller cells under high-glucose conditions[J]. Invest Ophthalmol Vis Sci, 2012, 53(2): 1023-1032. DOI: 10.1167/iovs.11-8695.

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The protective effect of Zhicao Tea Mixture on Müller cells and the expression of inflammatory factors in mice with diabetic retinopathy

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