| Background: Acne vulgaris is one of the most common chronic deforming skin diseases.The pathogenesis of acne is very complex,among which the increased activity of sebaceous glands and the vigorous lipid secretion affect all aspects of the pathogenesis of acne,so the regulation of sebaceous gland lipid secretion is an important way to treat acne.Endogenous androgens act on the Sterol Regulatory Element Binding Protein(SREBP)signaling pathway,causing to excessive secretion of lipids by sebaceous glands and inducing the occurrence or aggravation of acne.Emodin is derived from the traditional Chinese medicine rhubarb,which has the effects of inhibiting Propionibacterium acnes,inhibiting liver and vascular lipid deposition,antidepressant,and anti-tumor.Up to now,there is no relevant study on the effect of emodin on sebaceous glands.Sebaceous gland spots on the back of golden hamster are recognized as an ideal model for the study of acne sebaceous glands,so we chose this animal model to conduct related research.Objective: To investigate the effects of different concentrations of emodin cream on the proliferation and lipid secretion of sebaceous glands,Androgen Receptor(AR)and SREBP-1 expression in golden hamsters,and to explore the mechanism of emodin cream on sebaceous glands,so as to provide new ideas for the clinical treatment of acne.Methods:1.Emodin cream was prepared as low concentration,medium concentration,medium high concentration and high concentration(0.4mg/g、0.8mg/g、1.6mg/g、2.4mg/g).2.A total of 42 male golden hamsters of SPF class,age 6-7 weeks,weight 110±10 g were randomly devided into 7 groups: a blank group,a substrate group,an adapalene gel positive control group,a low concentration emodin cream group,a medium concentration emodin cream group,a medium high concentration emodin cream group,and a high concentration emodin cream group,with 6 golden hamsters in each group.The blank group didn’t give any treatment,while the substrate group was given substrate cream,the adapalene gel group was given adapalene gel,and the different concentrations of emodin groups were given low emodin cream,medium emodin cream,medium high emodin cream,and high concentration emodin cream.The medicine was applied locally to the lateral sebaceous glands on the back of golden hamsters and continued for 30 days,1 m L each time,twice daily.3.The appearance of sebaceous gland spots of golden hamsters was observed and photographed at 0,10,20 and 30 days,and the size of sebaceous gland spots in each group was measured by vernier caliper.4.On the 30 th day,the mice were sacrificed under anesthesia,and the skin tissue of sebaceous gland spots on the back of golden hamsters was collected and fixed in 4%formaldehyde fixative.5.The pathological changes of sebaceous gland spots were observed by HE staining.6.Oil red O staining was used to observe the lipid secretion of sebaceous glands.7.Immunohistochemical staining was used to detect the expression of PCNA and AR protein in sebaceous cells,and Image J software was used to analyze the data.8.RT-PCR was used to detect the expression of AR mRNA and SREBP-1 mRNA in sebaceous gland spots.Results:1.Comparing the appearance and size of the sebaceous gland spots of the golden hamster from different groups: the color of the sebaceous gland spots of the golden hamster before administration was similar,and there was no obvious difference in area.(P>0.05).As the administration time increased,size of the sebaceous gland spots of the blank group and the substrate group became increased and the color deepened gradually,and there was no obvious difference in the macular area of the sebaceous glands between the two groups.(P>0.05).The color of sebaceous gland spots in adapalene gel group and different concentrations of emodin cream groups became lighter,and the area of sebaceous gland spots decreased compared with the blank group,(P<0.05);After 30 days of treatment,the area of sebaceous gland spots in the high concentration emodin cream group was smaller than that in the adapalene gel group(P < 0.05),suggesting that emodin cream could inhibit the growth of sebaceous gland spots.2.Histopathological changes of sebaceous gland spots: after treatment,there was no significant difference in sebaceous gland structure between the blank group and the substrate group.Compared with the blank group,the adapalene gel group and each emodin group had thinner sebaceous gland thickness,smaller volume of gland lobe,fewer number and lobulation of gland spots,fewer overlapping layers of gland spots,and loosearranged sebaceous gland spots,especially in the high concentration of emodin cream group.3.Oil red O staining was used to observe the sebaceous gland lipid secretion in each group: the sebaceous gland lipid secretion in the blank group and the substrate group was vigorous.Compared with the blank group,the lipid secretion of sebaceous cells in adapalene gel group and different concentrations of emodin cream groups were reduced in varying degrees,and the lipid secretion of adapalene gel group and high concentration of emodin cream group was significantly reduced.4.The level of PCNA and AR protein in the sebaceous gland macular cells of each group were detected by immunogrouped staining: The level of PCNA and AR protein in the emodin cream groups at different concentration and the adapalene gel group were all significantly lower than that in the blank group,(P < 0.05),and the level of PCNA and AR protein in high concentration of emodin cream group were lower than those in adapalene gel group(P < 0.05).It is suggested that emodin cream can inhibit the proliferation of sebaceous gland cells and the expression of AR protein.5.RT-PCR was used to detect the expression of ARmRNA and SREBP-1mRNA in sebaceous gland spots of each group:(1)The levels of AR mRNA in the sebaceous macular tissue of the blank group were similar to the substrate group,with no statistical difference(P > 0.05).The level of AR mRNA in the sebaceous macular tissue of the adapalene gel group and the emodin cream group at each concentration except the medium high concentration group were lower than that of the blank group.(P < 0.05).The level of AR mRNA in the high concentration emodin cream group was lower than that in the adapalene gel group significantly(P <0.05).(2)The level of SREBP-1 mRNA in substrate group and blank group did not change significantly(P > 0.05).The level of SREBP-1 mRNA in the sebaceous macular tissue in emodin cream group and the adapalene gel group were significantly lower than that in the blank group.(P < 0.05).The level of SREBP-1 mRNA in high concentration emodin cream group was significantly lower than that in the adapalene gel group(P < 0.05).Conclusions:1.Topical emodin can inhibit the growth of sebaceous gland spots and the proliferation of sebaceous gland cells in golden hamsters,which may be related to the inhibition of AR.2.Topical emodin inhibits the synthesis and secretion of lipid in sebaceous gland spots of golden hamsters,which may be related to the decrease of SREBP-1 mRNA expression after inhibiting AR. |
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