[ ABSTRACT] AIM:To observe the change of skin histology in diabetic rats and to investigate the possible me-chanism of c-Jun N-terminal kinase (JNK) protein in the dorsal root ganglion (DRG) during the process.METHODS:Diabetic animal model was established in the male SD rats by intraperitoneal injection of streptozotocin.Plantar skin speci-mens of the rats were collected from control group, DM 2-week group (DM2), DM 4-week group (DM4), and DM 8-week group ( DM8) .Immunohistochemical staining and HE staining were used to observe the change of PGP 9.5 immunoreactive nerve terminals and the structures of the skin tissues.The protein expression of PGP 9.5 in the plantar skin tissues, and JNK and p-JNK protein in the DRG within lumbar 5, 6 (L5, 6), and sacral 1 (S1) spinal cord segments were detected by Western blotting.RESULTS:PGP 9.5 immunoreactive nerve terminals of the plantar skin of the rats mainly distributed in the basal layer of the epidermis and papillary dermis.Compared with control group, PGP 9.5 positive nerve terminals in DM4 group showed reduced density and sparse distribution.PGP 9.5 positive nerve terminals in DM8 group showed signifi-cantly reduced distribution, thinner nerve diameter, shorter length and distorted shape.Histological changes of the thinner epidermal tissue, reduced epidermal cell layers, uneven cell distribution and arrangement in DM4 group, and significantly reduced epidermal cell layers, swollen and blurred cells, increasing cell gap, lack of stratified epidermis arrangement for part of epidermis, atropal and degenerated dermal collagen fiber, significantly decreased subcutaneous fat in DM8 group were observed.The results of Western blotting showed that the protein expression of PGP 9.5 in the plantar skin tissue of DM rats was progressively decreased along with the disease, while the protein level of p-JNK in L5, 6-DRG or S1-DRG showed a gradual increasing trend.PGP 9.5 immunoreactive positive nerve terminal density of plantar skin in DM rats had a negative correlation with the protein level of p-JNK in L5, 6-DRG and S1-DRG (P<0.01), but showed a significant positive correlation with the plantar skin thickness (P<0.01).CONCLUSION:The protein level of p-JNK within L5, 6-DRG or S1-DRG in DM rats shows a progressive enhancement.At the same time, there is a significant change in the skin tissue density and structure.The changes of skin tissue and nerve morphology in DM rat may be related to the activation of JNK/SAPK pathway in L5, 6-DRG or S1-DRG cells.Blocking or inhibiting JNK/SAPK pathway may delay the diabetic pe-ripheral neuropathy and reduce the risk of skin lesions.%目的：观察糖尿病（ DM）大鼠皮肤组织学改变，探讨背根神经节（ DRG）内c－Jun氨基端激酶（ JNK）蛋白在其中的可能作用机制。方法：雄性SD大鼠腹腔注射链脲佐菌素制备DM模型，分别取正常对照（control）组、DM 2周（DM2）组、DM 4周（DM4）组和DM 8周（DM8）组大鼠足底皮肤标本进行PGP 9.5免疫组化染色和HE染色，观察皮肤PGP 9.5免疫阳性神经末梢和皮肤组织结构变化；同时采用Western blotting法分别检测上述各组大鼠足底皮肤组织内PGP 9.5蛋白和脊髓腰5～6（L5，6）、骶1（S1）节段DRG内JNK和p-JNK蛋白的表达。结果：大鼠足底皮肤PGP 9.5免疫阳性神经末梢主要分布于表皮基底层和真皮乳头层，与正常对照组比较，DM4组大鼠表皮阳性神经末梢密度减少，分布稀疏，DM8组大鼠表皮阳性神经末梢分布明显减少，神经直径变细，长度变短，走形扭曲；组织学观察可见，DM4组大鼠表皮组织变薄，表皮细胞层次减少，细胞分布及排列不均匀，DM8组大鼠表皮细胞层次明显减少，细胞肿胀模糊，细胞间隙增大，部分表皮缺乏复层排列，真皮层胶原纤维萎缩、变性，皮下脂肪明显减少。蛋白印迹检测发现皮肤组织内PGP 9.5蛋白的表达随病程呈渐进性减弱；同时L5，6-DRG和S1-DRG内p-JNK蛋白的水平呈现渐进性增强趋势。 DM大鼠皮肤PGP 9.5免疫阳性神经末梢吸光度值与L5，6-DRG和S1-DRG内的p-JNK蛋白灰度值之间呈负相关（P＜0.01）；与表皮厚度值之间呈显著正相关。结论：DM大鼠皮肤组织和皮肤神经均存在明显形态结构改变，同时存在L5，6-DRG和S1-DRG内p-JNK蛋白的渐进性高表达， DM大鼠皮肤PGP 9.5免疫阳性神经末梢密度变化与L5，6-DRG和S1-DRG内p-JNK蛋白水平的变化之间呈负相关；与表皮厚度的变化呈显著正相关。皮肤神经形态结构的改变可能与背根神经节细胞JNK／SAPK通路活化有关，阻断或抑制JNK／SAPK通路可以起到延缓糖尿病周围神经病变，减轻皮肤组织病变发生的作用。
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