Zhang J Y, Li F L, Wang H, Li Y
Department of Prosthodontics, Shanxi Provincial People's Hospital & The Fifth Clinical Medical College of Shanxi Medical University, Taiyuan 030000, China.
Zhonghua Kou Qiang Yi Xue Za Zhi. 2022 Sep 9;57(9):938-945. doi: 10.3760/cma.j.cn112144-20220129-00036.
To study the effect of gastrodin on oxidative stress and bone tissue around implants in type 2 diabetes mellitus rats (T2DM), so as to provide therapeutic basis for the problems of poor osseointegration and long repair period of implants in type 2 diabetic patients, to provide the basis for the development of new therapeutic drugs. Forty SD rats aged 5 weeks were divided into control group (=10) and model group (=30). The model group was fed with high glycolipid diet for 4 weeks and injected with 35 mg/kg streptozocin. The T2DM were divided into diabetic group (=10) and gastrodin group (=10). Pure screw titanium implants were placed in the metaphysis of both tibia. Rats in gastrodin group were given gastrodin 13.6 mg/kg everyday, while the control group and diabetic group were given the same dose of saline solution. Blood glucose was measured every two weeks after operation in all rats. After 4 and 8 weeks, the contents of serum malondialdehyde (MDA) and superoxide dismutase (SOD) were measured to analyze the oxidative stress level in rats. The expression of anti-apoptosis protein [B cell lymphoma/lewkmia-2 (bcl-2)]and apoptosis protein [bcl-2-associated X protein (bax)] was analyzed by immunohistochemistry. HE staining and micro-CT scanning were used to analyze the osseointegration around the implants. The blood glucose of gastrodin [(12.98±2.53), (13.64±1.96), (14.58±3.40) and (12.84±2.82) mmol/L] were significantly lower than that of diabetic group [(20.97±2.27), (17.94±3.76), (23.66±2.90) and (21.22±2.67) mmol/L] at corresponding time point (<0.017). Four and 8 weeks following surgery, the MDA concentration in gastrodin group [(5.21±1.60) and (3.47±1.17) nmol/ml] was significantly lower than that in diabetic group [(11.42±5.11) and (7.31±1.37) nmol/ml] at the corresponding time points (<0.017), while SOD activity in gastrodin group [(42.89±6.00) and (53.12±9.73) U/ml] was significantly higher than those in diabetic group [(27.09±6.11) and (32.08±2.97) U/ml] at the corresponding time points (<0.017). Immunohistochemistry showed that the bcl-2 expression in gastrodin group was significantly higher than that in diabetic group at 4 and 8 weeks following surgery (<0.017), while the bax expression in gastrodin group was significantly lower than that in diabetic group (<0.017). Four weeks after surgery, the bone volume/tissue volume (BV/TV), connection density (Conn.D), trabecular number (Tb.N), trabecular thickness (Tb.Th) in gastrodin group were significantly higher than those in diabetic group (<0.017). There was no significant difference in trabecular separation/spacing (Tb.sp) between gastrodin group and diabetic group (<0.017). Eight weeks after surgery, the BV/TV, Tb.N in gastrodin group were significantly higher than those in the diabetic group (<0.017). There was no significant difference in Conn.D between gastrodin group and diabetic group (<0.017). There was no significant difference in Tb.Th and Tb.sp in three groups (<0.017). The trabecular structure in gastrodin group was better than that in diabetic group by HE staining. Gastrodin can decrease blood glucose, improve oxidative stress, protect bone tissue from apoptosis and promote bone formation around implants in T2DM.
为研究天麻素对2型糖尿病大鼠（T2DM）种植体周围氧化应激及骨组织的影响，为解决2型糖尿病患者种植体骨结合不良、修复周期长的问题提供治疗依据，为开发新的治疗药物提供依据。将40只5周龄的SD大鼠分为对照组（n = 10）和模型组（n = 30）。模型组给予高糖高脂饮食4周，然后注射35 mg/kg链脲佐菌素。将T2DM大鼠分为糖尿病组（n = 10）和天麻素组（n = 10）。将纯钛螺纹种植体植入双侧胫骨的干骺端。天麻素组大鼠每天给予13.6 mg/kg天麻素，对照组和糖尿病组给予相同剂量的生理盐水。术后所有大鼠每两周测量一次血糖。术后4周和8周，检测血清丙二醛（MDA）和超氧化物歧化酶（SOD）含量，分析大鼠氧化应激水平。采用免疫组织化学法分析抗凋亡蛋白[B细胞淋巴瘤/白血病-2（bcl-2）]和凋亡蛋白[bcl-2相关X蛋白（bax）]的表达。采用苏木精-伊红（HE）染色和显微CT扫描分析种植体周围的骨结合情况。天麻素组各时间点血糖[（12.98±2.53）、（13.64±1.96）、（14.58±3.40）和（12.84±2.82）mmol/L]均显著低于糖尿病组[（20.97±2.27）、（17.94±3.76）、（23.66±2.90）和（21.22±2.67）mmol/L]（P<0.017）。术后4周和8周，天麻素组相应时间点MDA浓度[（5.21±1.60）和（3.47±1.17）nmol/ml]显著低于糖尿病组[（11.42±5.11）和（7.31±1.37）nmol/ml]（P<0.017），而天麻素组相应时间点SOD活性[（42.89±6.00）和（53.12±9.73）U/ml]显著高于糖尿病组[（27.09±6.11）和（32.08±2.97）U/ml]（P<0.017）。免疫组织化学显示，术后4周和8周天麻素组bcl-2表达显著高于糖尿病组（P<0.017），而天麻素组bax表达显著低于糖尿病组（P<0.017）。术后4周，天麻素组骨体积/组织体积（BV/TV）、连接密度（Conn.D）、骨小梁数量（Tb.N）、骨小梁厚度（Tb.Th）均显著高于糖尿病组（P<0.017）。天麻素组与糖尿病组骨小梁间距（Tb.sp）差异无统计学意义（P<0.017）。术后8周，天麻素组BV/TV、Tb.N显著高于糖尿病组（P<0.017）。天麻素组与糖尿病组Conn.D差异无统计学意义（P<0.017）。三组Tb.Th和Tb.sp差异无统计学意义（P<0.017）。HE染色显示天麻素组骨小梁结构优于糖尿病组。天麻素可降低T2DM大鼠血糖，改善氧化应激，保护骨组织免受凋亡，并促进种植体周围骨形成。
