Golderman Valery, Berkowitz Shani, Guly Gofrit Shani, Gera Orna, Aharoni Shay Anat, Zohar Daniela Noa, Keren Daria, Dori Amir, Chapman Joab, Shavit-Stein Efrat
Department of Neurology, The Chaim Sheba Medical Center, Ramat Gan 52626202, Israel.
Department of Neurology and Neurosurgery, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
Biomedicines. 2022 Jun 20;10(6):1461. doi: 10.3390/biomedicines10061461.
Thrombin is present in peripheral nerves and is involved in the pathogenesis of neuropathy. We evaluated thrombin activity in skin punch biopsies taken from the paws of male mice and rats and from the legs of patients with suspected small-fiber neuropathy (SFN). In mice, inflammation was induced focally by subcutaneous adjuvant injection to one paw and systemically by intraperitoneal lipopolysaccharides (LPS) administration. One day following injection, thrombin activity increased in the skin of the injected compared with the contralateral and non-injected control paws ( = 0.0009). One week following injection, thrombin increased in both injected and contralateral paws compared with the controls ( = 0.026), coupled with increased heat-sensitivity ( = 0.009). Thrombin activity in the footpad skin was significantly increased one week after systemic administration of LPS compared with the controls ( = 0.023). This was not accompanied by increased heat sensitivity. In human skin, a correlation was found between nerve fiber density and thrombin activity. In addition, a lower thrombin activity was measured in patients with evidence of systemic inflammation compared with the controls ( = 0.0035). These results support the modification of skin thrombin activity by regional and systemic inflammation as well as a correlation with nerve fiber density. Skin thrombin activity measurments may aid in the diagnosis and treatment of SFN.
凝血酶存在于外周神经中，并参与神经病变的发病机制。我们评估了从雄性小鼠和大鼠爪部以及疑似小纤维神经病变（SFN）患者腿部获取的皮肤打孔活检组织中的凝血酶活性。在小鼠中，通过向一只爪部皮下注射佐剂局部诱导炎症，并通过腹腔注射脂多糖（LPS）全身诱导炎症。注射后一天，与对侧未注射的对照爪相比，注射部位皮肤中的凝血酶活性增加（P = 0.0009）。注射后一周，与对照相比，注射爪和对侧爪中的凝血酶均增加（P = 0.026），同时热敏感性增加（P = 0.009）。与对照相比，全身注射LPS一周后足垫皮肤中的凝血酶活性显著增加（P = 0.023）。但这并未伴随热敏感性增加。在人体皮肤中，发现神经纤维密度与凝血酶活性之间存在相关性。此外，与对照相比，有全身炎症证据的患者凝血酶活性较低（P = 0.0035）。这些结果支持局部和全身炎症对皮肤凝血酶活性的调节以及与神经纤维密度的相关性。皮肤凝血酶活性测量可能有助于SFN的诊断和治疗。
