| 摘要: | 賽滅寧（cypermethrin, CYP）是廣泛用於害蟲防治的合成除蟲菊精農藥之一，飲食暴露CYP會累積在脂肪和皮膚毛髮中，並增加體內氧化壓力導致發炎反應。肥胖是世界各國普遍存在的健康問題，與慢性發炎反應有關，會增加乾癬皮膚疾病的罹患率和嚴重程度。本研究使用高脂飲食誘發肥胖的小鼠模式，探討飲食暴露低劑量CYP對肥胖以及肥胖合併乾癬小鼠皮膚健康之影響。本實驗使用雄性C57BL/6小鼠，將小鼠隨機分成C組（一般飼料對照組）、HF組（高脂飼料對照組）、HFC組（高脂飼料CYP暴露組）、HFP組（高脂飼料乾癬組）和HFCP組（高脂飼料CYP暴露乾癬組），每組10隻小鼠。C組餵食AIN-93M飼料；HF組和HFP組餵食脂肪含量占總熱量50%的高脂飼料；HFC組和HFCP組餵食含有CYP 35 ppm（相當於5 mg CYP/kg body weight/day）的高脂飼料。飲食介入第38天開始，連續5天於HFP組和HFCP組小鼠的背部皮膚塗抹含有5% imiquimod的Aldara乳膏誘發乾癬樣皮膚炎，C組、HF組、HFC組則塗抹Vanicream乳霜作為對照。所有小鼠在飲食介入第43天犧牲，收集血液、副睪脂肪及背部皮膚進行分析。結果顯示，與HF組相比，HFC組小鼠血漿中葡萄糖（glucose, GLU）及高密度脂蛋白（high-density lipoprotein, HDL）濃度降低，睪固酮濃度增加；血液嗜中性白血球比例增加，促發炎單核球、抗發炎單核球及B細胞比例降低；副睪脂肪中脂聯素之messenger RNA (mRNA)表現量下降，steroid 5-alpha reductase 1 的mRNA表現量上升。與HFP組相比，HFCP組皮膚厚度增加；血漿中GLU、總膽固醇和HDL濃度降低，睪固酮濃度增加；血液中Treg比例增加；副睪脂肪中巨噬細胞比例增加，瘦體素之mRNA表現量下降；而皮膚嗜中性白血球比例及defensin beta 4 的mRNA表現量上升，組織切片可看出有表皮潰瘍伴隨真皮發炎的病徵，但Baker’s score與HFP組相比沒有差異。本研究結果顯示，肥胖以及肥胖合併乾癬小鼠經由飲食暴露低劑量的CYP，會影響血液中GLU、脂質和睪固酮濃度，以及白血球分佈；CYP對於肥胖小鼠的皮膚健康沒有負面影響，然而CYP會促使嗜中性白血球聚集至肥胖合併乾癬小鼠的皮膚，導致皮膚發炎的情況更為嚴重。
Cypermethrin (CYP) is one of the widely used pyrethroids to prevent from pests. CYP from dietary exposure may accumulate in fat and skin hair and increase oxidative stress, leading to inflammation. Obesity, a common health problem worldwide, is associated with chronic inflammation and increases the incidence and severity of psoriasis. This study investigated the effects of dietary exposure to low doses CYP on the skin health in obese mice induced by high-fat diets and obese mice combined with psoriasis-like dermatitis. Male C57BL/6 mice were randomly assigned into the C group (the control diet), the HF group (the high-fat diet control), the HFC group (high-fat diet containing CYP), the HFP group (high-fat diet with psoriasis induction), and the HFCP group (high-fat diet containing CYP and psoriasis induction). Ten mice were included in each group. The C group was fed an AIN-93M diet. The HF group and the HFP group were fed a high-fat diet containing 50% of total calories from fat, and the HFC group and the HFCP group were given a high-fat diet containing 35 ppm CYP (5 mg/kg body weight/day). On day 38 of the dietary intervention, the Aldara cream containing 5% imiquimod was applied to the back skin of mice in the HFP group and the HFCP group for 5 consecutive days to induce psoriasis-like dermatitis whereas the Vanicream cream was applied to mice in the C group, the HF group, and the HFC group as a control. All mice were sacrificed on day 43 of the dietary intervention. Whole blood, the epididymal fat and the back skin were collected for analysis. The results showed that compared with the HF group, mice in the HFC group had lower glucose (GLU) and high-density lipoprotein (HDL) concentrations but higher testosterone concentrations in plasma. Blood neutrophil population was increased, and the percentages of pro-inflammatory monocytes (Mo), anti-inflammatory Mo, and B cells in blood were decreased. The messenger RNA (mRNA) expression level of adiponectin was reduced whereas the mRNA expressions of steroid 5-alpha reductase 1 was upregulated in the epididymal fat. Compared with the HFP group, the back skin thickness was increased in the HFCP group. Mice in the HFCP group had lower GLU, total cholesterol and HDL levels, but higher testosterone concentrations in plasma. The percentage of blood regulatory T cells was elevated. The macrophage population was increased whereas the mRNA expression level of leptin was decreased in the epididymal fat. Neutrophil infiltration into the skin and the mRNA expressions of defensin beta 4 were enhanced. The skin tissue sections showed epidermal ulceration with dermal inflammation. However, there was no difference in the Baker's score between the HFP group and the HFCP group. These findings suggest that dietary exposure to low doses CYP affects the blood GLU, lipid and testosterone contents, and the distribution of circulating white blood cells in obese mice with or without psoriasis-like dermatitis. CYP has no adverse effects on skin health in obese mice. However, CYP promotes neutrophil infiltration into the skin of obese mice with psoriasis-like dermatitis, which aggravates skin inflammation. |
