於囓齒類神經損傷時之汗腺神經退化研究

失去分泌汗液功能是數個神經病變中的重要指標之一，例如：自主神經病變和糖尿病神經病變等。在之前的研究中，我們的實驗室已經建立了一套以面積為基準的支配汗腺神經定量方法，去探討在人類糖尿病的神經病變中，支配汗腺的神經分布，稱做汗腺神經支配指數〈SGII〉。而此篇研究旨在﹝1﹞研究神經損傷之後，汗腺的支配神經分布﹝2﹞探究分泌汗液的神經退化，對於汗腺的影響。我們利用大鼠為動物模式，橫斷坐骨神經至第七天的手術，發現在第七天的神經橫斷時，坐骨神經的神經纖維，從遠端到截斷處都已完全退化，我們利用坐骨神經的半薄片染色以及神經傳導的實驗去驗證。汗腺神經支配指數〈SGII〉的數值在手術側有明顯的下降﹝0.146 ± 0.011 vs. 0.015 ± 0.003, p < 0.0001﹞，而同樣的結果，也在表皮神經纖維密度〈IENFD〉實驗中被發現。在肌肉的神經退化研究中，肌肉萎縮是一個眾所皆知的現象和問題。進一步，我們探討汗腺的萎縮，是否會在神經退化的情況下發生。在坐骨神經截斷兩週的老鼠腳掌上，我們發現分泌汗腺的管壁，在手術側有明顯變薄﹝0.215 ± 0.015 vs. 0.163 ± 0.004 μm, p = 0.032﹞同樣地，分泌汗腺管壁内徑與管壁直徑的比值，是在手術側增加的﹝0.160 ± 0.005 v.s. 0.270 ± 0.025μm, p = 0.013﹞這些觀察顯示，神經截斷導致的汗腺萎縮情形，是因汗腺分泌管壁的增加所造成。我們進一步探討泌汗神經退化的相關分子機制，我們發現磷酸化的細胞外訊息轉導酶﹝pERK﹞的免疫反應和神經纖維結構蛋白﹝PGP9.5﹞會在相同的位置表現，且在神經截斷之後有顯的減少。另一方面，我們發現轉錄因子﹝c-fos﹞的免疫反應，會在神經退化後在汗腺的管壁上，有顯著的增加。

關鍵字

汗腺；神經損傷；神經退化；萎縮；腳掌

並列摘要

Sudomotor failure is an important presentation of several neuropathies, such as autonomic neuropathy and diabetic neuropathy. In previous studies, our lab has established an area-based morphometry to quantify sweat gland innervations in human diabetic neuropathy, called sweat gland innervations index (SGII). This study aimed (1) to examine sweat gland innervation after nerve injury and (2) to explore the effect of sudomotor denervation on sweat glands. We applied a transection model of the sciatic nerve on rats. On day 7 of transection, nerve fibers distal to the transection were completely degenerated as validated with on semi-thin sections of the sciatic nerve and nerve conduction studies. Values of sweat gland innervations index (SGII) were significantly reduced (0.146 ± 0.011 vs. 0.015 ± 0.003, p < 0.0001). So was intra-epidermal nerve fiber density (IENFD) on operated side foot pad. In denervation study on muscle, atrophy is one well known phenomena and issue. We then asked whether sweat gland atrophy occurred after denervation. Two weeks after sciatic nerve transection, the wall thickness of sweat gland coils was significantly reduced (0.215 ± 0.015 vs. 0.163 ± 0.004 μm, p = 0.032). Accordingly, the ratio of the lumen to the diameter of the sweat gland coil was increased (0.160 ± 0.005 v.s. 0.270 ± 0.025 μm, p = 0.013). These observations indicated nerve transection-induced targeted atrophy due to increase of sweat gland coil lumen. We, to investigate the molecular mechanism of denervation, further explored molecular candidates of sudomotor denervation. pERK-immunoreactivity was co-localized with protein gene product 9.5 (PGP9.5) but reduced after nerve transection. However, c-fos-immunoreactivity was increased in sweat gland coils after denervation.

並列關鍵字

Sweat gland ； nerve injury ； denervation ； atrophy ； footpad

參考文獻

Ahn, M., Moon, C., Lee, Y., Koh, C.S., Kohyama, K., Tanuma, N., Matsumoto, Y., Kim, H.M., Kim, S.R., Shin, T., 2004. Activation of extracellular signal-regulated kinases in the sciatic nerves of rats with experimental autoimmune neuritis. Neuroscience letters. 372, 57-61.

Avellino, A.M., Hart, D., Dailey, A.T., MacKinnon, M., Ellegala, D., Kliot, M., 1995. Differential macrophage responses in the peripheral and central nervous system during wallerian degeneration of axons. Exp Neurol. 136, 183-98.

Baser, S.M., Meer, J., Polinsky, R.J., Hallett, M., 1991. Sudomotor function in autonomic failure. Neurology. 41, 1564-6.

Biemond, A., Beck, W., 1955. neural muscle atrophy with degeneration of the substantia nigra. Confin Neurol. 15, 142-53.

Bloomgarden, Z.T., 2008. Diabetic nephropathy. Diabetes Care. 31, 823-7.

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於囓齒類神經損傷時之汗腺神經退化研究

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