| 1Purpose: Discussing the anti-inflammatory effect of probucol on non-proli-ferative diabetic retinopathy, studying the molecule mechanism in the early medicat-ion of diabetic retinopathy by using probucol.2Methods: Subjects were90patients with2-type non-proliferative diabeticretinopathy in our ophthalmic department from March2010to June2010. Thesubjects were divided into2groups according to parallel control, random, single blindand simulation methods:(1) control group (45subjects): diet+sports guiding+intensified hypoglycemic medication(FPG<6.lmmol/L, HbA1c<6.5%, BP<130/80mmHg)+placebo (taking3tablets twice daily after breakfast and supperrespectively);(2) probucol group (45subjects): diet+sports guiding+intensifiedhypoglycemic medication (FPG<6.lmmol/L,HbA1c<6.5%,BP<130/80mmHg)+probucol(taking3tablets twice daily after breakfast and supper respectively); at thesame time collecting45healthy volunteers with consistent basic information. The agerange of subjects in the experiment ranges was60-70. Two groups of treatment time:11.5~12months.(1) all of the90patients with2-type non-proliferative diabeticretinopathy took physical examination on the first day of being grouped (including:blood suger blood pressure, HbA1c, total cholesterol, LDL, liver function, kidneyfunction, ECG) and examination of eyes (including the best corrected visual acuity,slit-lamp microscopic examination, intraocular pressure, direct and indirectophthalmoscope inspection, ocular fundus photography and FFA examination).According to our established rating standard of the physical sign of ocular fundus,combining the ocular fundus examination and fundus fluorescein radiography, werated for the ocular fundus of all the patients in the beginning of grouping and at theend of the experiment. In addition, all the patients took non anti-freezing venousblood examinations on next day morning after8-10h fast both in the beginning of grouping and at the end of the experiment. The blood serum was centrifuged fromblood sample for20min at low temperature (3000rPm), and sealed and stored inrefrigerator at-80℃for measuring the absorbance value of hs-CRP, IL-6, TNF-a,VEGF and calculating its concentration of blood serum. During the whole period ofmedication, all the patients with non-proliferative diabetic retinopathy monitored andrecorded their own blood sugar and blood pressure every day. The doctor ofendocrinology division helped the patients who were not qualified for the intensifiedstandard reach the standard; one physical examination every three months for makingcomparison (including: LDL,TC, HbA1c, liver function,kidney function, ECG, thebest corrected visual acuity, slit-lamp microscopic examination, direct and indirectocular fundus examination, intraocular pressure ocular fundus photography etal).During the period of treatment,2groups of patients with reject or shedding standardsshould be removed. For the patients with aggravated disease and in need of retinalphotocoagulation or surgical treatment were included in the experiment’s statistics,for the patients excluded from the experiment due to other reasons were not includedin the statistics. But all the patients with probucol treatment were recorded for theuntoward effect and included in the statistic analysis of probucol’s side effect. At thesame time, all the patients with non-proliferative diabetic retinopathy were randomlyand frequently observed by the doctor from endocrinology division.(2) the collected45healthy volunteers took examination of blood sugar, blood pressure, HbA1c, totalcholesterol, LDL and the bloody serum concentration of hs-CRP,IL-6,TNF-a,VEGFby taking non anti-freezing venous blood examination in the morning of next dayafter8-10h fast.3Results:（1） The control group and probucol group after treatment, FPG, SBP andHbA1C levels are obviously lower than those before the intervention (P<0.05); aftertreatment, the comparison between the two groups is no statistical difference(P>0.05);which suggests that the level of FPG, SBP and HbA1C were steadily controlled duringthe whole process. There is no significant change of TC, LDL levels before and after treatment in the the control group (P>0.05); and probucol group after treatment, theTC, LDL levels are lower than before treatment (P<0.05), and probucol group aftertreatment, the TC, LDL levels are lower than those of the control group (P<0.05),with a statistical significance. Indicating: probucol can reduce the level of TC andLDL of patients with diabetic retinopathy.（2）Before treatment, the hs-CRP, IL-6, TNF-a and VEGF in the control groupand probucol group are significantly higher than those of the normal group (P<0.01),linear correlation analysis showed that the rating results of non-proliferative diabeticretinopathy was positively correlated with the levels of four cytokine (P<0.05),which suggests that the happening mechanism of non-proliferative diabeticretinopathy was closely related with the organ’s inflammation. After probucoltreatment, the levels of hs-CRP, IL-6, TNF-a and VEGF were significantly lower thanbefore treatment (P<0.01), the levels of hs-CRP, IL-6, TNF-a and VEGF in probucolgroup were significantly lower than those of control group (P<0.01), which suggeststhat probucol can reduce the level of hs-CRP, IL-6, TNF-a and VEGF of patients withdiabetic retinopathy.（3）At the final follow-up, the visual acuity and fundus of patients in thecontrol group is not obviously better than before; the visual acuity and fundus of thepatients in probucol group was significantly better than that before treatment P<0.01,which suggested that probucol could improve the visual acuity and fundus ofnon-proliferative diabetic retinopathy patients. The total effectiveness in probucolgroup was86.8%, and17.6%for control group, which was significantly different.This suggested that probucol’s anti-inflammatory effect could improve the visualacuity and ocular fundus of non-proliferative diabetic retinopathy patients on the basisof intensified treatment of lowering blood sugar, blood pressure and improvingHbA1c.（4）During the follow-up period, there were not aberration of blood routine, urineroutine, liver and kidney function,ECG in probucol group, except for only onepatient with slight diarrhea and flatulence, but these symptoms was disappearedwhen continue to eat drag. This suggested that the effect of probucol is safe and reliable.4Conclusions: Under the condition of stable blood sugar, blood pressure andHbA1c, probucol can effectively reduce the level of TC, LDL, cytokine (hs-CRP,IL-6, VEGF, TNF-a) in patients with nonproliferative diabetic retinopathy, andimprove their visual acuity and eye fundus of the patients with type2nonproliferativediabetic retinopathy. This suggests that porbucol was not only beneficial for bloodlipid, but also strong in anti-inflammation. The mechanism of probucol treatingnon-proliferative diabetic retinopathy are possible relative to its anti-inflammatoryeffect. |
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