血府逐瘀湯對糖尿病周邊神經病變效用之研究：一個隨機、雙盲、安慰劑──對照組的臨床試驗

A Study of the Effects of Xie-Fu-Zhu-Yu-Tang on Diabetic Peripheral Neuropathy: A Randomized, Double Blind, Placebo–Controlled Clinical Trial

代謝異常和血管病變已被認為是引起糖尿病周邊神經病變的主要因素，糖尿病周邊神經病變屬於傳統中醫血瘀證的範圍，血府逐瘀湯是活血化瘀的代表方劑之一。因此本研究的目的是為了探討血府逐瘀湯對糖尿病周邊神經病變的療效，選擇86位糖尿病的患者，他們的正中神經感覺和運動、深腓神經的運動，以及腓腸神經的感覺神經的最大傳導速度中，其中至少有一項低於正常值下限的80%％以下，根據有無中醫辨證分成無辨證組和氣血瘀阻型組。我們設計一個隨機、雙盲、placebo–controlled，十二星期的臨床試驗，分別施予血府逐瘀湯、Gabapentin、methycobal和Placebo（大麥麩）。療效評估是根據試驗前後body mass index（BMI）、空腹血糖（FBG）、糖化血色素（HbA1C）、Alanine aminotransferase （SGPT）、Creatinine（Cr）、Triglyceride （TG ）、Total cholesterol（TC）、High density lipoprotein–cholesterol（HDL–C）、收縮血壓（SBP）、舒張血壓（DBP）、神經傳導速度（NCV）、神經症狀（手足麻木、手足無力、疼痛、冰冷、頭暈眼花、全部症狀）、生活品質量表（生理功能、身體疼痛、自覺健康、活力狀態、社會功能、心理健康）。結果顯示血府逐瘀湯和Gabapentin相似，兩者都能改善糖尿病周邊神經病變的正中神經感覺、運動和深腓神經的運動神經，和腓腸神經的最大神經傳導速度。血府逐瘀湯和Gabapentin兩者也能有改善手足麻木和疼痛。血府逐瘀湯對生理功能和心理健康有改善作用，Gabapentin則無，但兩者對於自覺健康和活力狀態都有改善的作用。對於氣血瘀阻型糖尿病周邊神經病變，血府逐瘀湯和Gabapentin能改善手足麻木，但對於手足無力、冰冷、疼痛、頭暈眼花、全部症狀，兩者和Methycobal、Placebo相似都沒有作用。血府逐瘀湯對自覺健康有改善作用，但對生理功能、身體疼痛、活力狀態、社會功能，以及心理健康則沒有作用。結論是血府逐瘀湯能改善糖尿病周邊神經病變的神經傳導速度、改善手足麻木和疼痛，以及改善生活品質。又血府逐瘀湯連續服用十二星期，對血糖、血壓、肝、腎功能沒有影響，因此我們認為血府逐瘀湯用來治療糖尿病的周邊神經病變是有效而且安全的。糖尿病周邊神經病變在本質上屬於血瘀，因此可用活血化瘀的藥物或方劑來治療如血府逐瘀湯。

It is believed that both metabolic and vascular factors contribute to development of peripheral neuropathy in diabetes. Traditional Chinese Medicine believes that diabetic peripheral neuropathy involves blood stasis; Xie-Fu-Zhu-Yu-Tang (Xi) is one of representative formulae used to quicken the blood and dispel such stasis. Therefore, the aim of the present study was to investigate effects of Xi on diabetic peripheral neuropathy. A total of 86 diabetic patients were involved in the study and all patients had at least one maximal nerve conduction velocity in the right median nerve, deep peroneal nerve or sural nerve at <80% of the normal value. We designed a randomized, double blind, placebo-controlled, 12 weeks clinical trial. Xi, Gabapentin (Ga), Methycobal (Me) and a control group consisting of powdered barley (Co) were administrated to the 4 various groups. The effect of the various treatments were measured by analyzing changes in body mass index (BMI), fasting blood sugar (FBS), glycosolated hemoglobin (HbA1C), GPT, Cretinine (Cr), Triglycerides (TG), total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), systolic blood pressure, diastolic blood pressure, nerve conduction velocity, nerve related symptoms including numbness of the hands or feet, weakness of hands or feet, pain, cold sensations, dizziness and finally the overall effect of the symptoms on the patient’s quality of life including physiological function, body pain, selfhealth, activity, social functionality and psychological health. The results indicated that the Xi, Ga, Me and Co groups showed no significant changes in BMI, FBG, HbA1C, GPT, Cr, HDL-C, SBP, DBP. However, both Xi and Ga increased maximal nerve conduction velocity and improved the patients’ symptoms in terms of numbness and pain. Xi also improved the patients’ physiological and psychological health, but this did not occur with the Ga group. When diabetic peripheral neuropathy is considered in terms of the Qi-Blood stasis block pattern, both Xi and Ga improved numbness of hands and feet, but did not improve weakness of hands and feet, cold sensations, body pain, dizziness, and overall symptoms, which were similar across all four groups. Nonetheless, Xi did improved self-health, but did not improve physiological functioning, body pain, activity, social functioning and psychological functioning. In conclusion, Xi can increase maximal nerve conduction velocity and also can improve numbness of hands and feet, reduce pain and help with a better quality of life. In addition, continuous administration of Xi for 12 weeks did not change FBS, BP, liver and renal function. Therefore, we consider that Xi is effective and safe for use in the treatment of diabetic peripheral neuropathy. This supports the idea that diabetic peripheral neuropathy belongs in Chinese Medicine to the blood stasis group and therefore should be treated by a blood quickening and stasis dispelling formula such as Xi.