目的 通過構(gòu)建糖尿病腎?。―N）大鼠模型，研究環(huán)孢素A對DN大鼠足細(xì)胞氧化應(yīng)激損傷的影響。方法 將30只SPF級SD大鼠隨機(jī)分為對照組、模型組和環(huán)孢素A組，每組10只。通過高糖高脂飼料聯(lián)合鏈脲佐菌素（STZ）建造大鼠DN大鼠模型（ip 40 mg/kg 1%鏈脲佐菌素）。建模4周后，環(huán)孢素A組大鼠ig 3 mg/kg環(huán)孢素A，1次/d，連續(xù)給藥4周，其余兩組ig等量飲用水。記錄大鼠體質(zhì)量，尿蛋白測定試劑盒檢測24 h尿蛋白，全自動血糖儀檢測空腹血糖（FBG）；AU480全自動生化分析儀檢測血肌酐（Scr）和尿素氮（BUN）；化學(xué)熒光法檢測活性氧（ROS）；化學(xué)比色法檢測過氧化物歧化酶（SOD）活性；硫代巴比妥酸比色法檢測丙二醛（MDA）水平；Western blotting檢測腎組織nephrin、p38 MAPK和p-p38 MAPK蛋白表達(dá)水平。結(jié)果 與對照組相比，模型組大鼠體質(zhì)量明顯減輕，24 h尿蛋白、FBG、Scr、BUN、ROS水平和MDA含量顯著增加，nephrin、p38 MAPK和p-p38 MAPK蛋白表達(dá)顯著增加，而SOD活性明顯降低（P＜0.05、0.01）。與模型組相比，環(huán)孢素A組大鼠體質(zhì)量顯著增加，24 h尿蛋白、Scr、BUN、ROS水平及MDA含量顯著降低，nephrin、p38 MAPK和p-p38 MAPK蛋白表達(dá)顯著降低，而SOD活性明顯升高（P＜0.05、0.01）。結(jié)論 環(huán)孢素A可能通過調(diào)控p38 MAPK信號通路抑制氧化應(yīng)激，改善DN大鼠腎組織足細(xì)胞損傷，緩解DN大鼠病情進(jìn)展。

Objective To study the effect of cyclosporine A on oxidative stress injury of podocytes in a diabetic nephropathy (DN) rats model.Methods 30 SPF SD rats (10 rats in each group) were randomly divided into control group, model group and cyclosporine A group. The rat model of diabetic nephropathy was established by high-sugar and high-fat diet combined with streptozotocin (STZ) (40 mg/kg ip 1% streptozotocin). After 4 weeks of modeling, the rats in cyclosporine A group were intragastrically administered with cyclosporine A of 3 mg/kg, once daily for 4 weeks, and the other two groups were given the same amount of drinking water. The body mass of rats was recorded, 24 h urinary protein, fasting blood glucose (FBG), serum creatinine (Scr) and blood urea nitrogen (BUN) were measured by urine protein determination Kit, automatic blood glucose analyzer, reactive oxygen species (ROS) were detected by chemical fluorescence method, superoxide dismutase (SOD) was detected by chemical colorimetry, malondialdehyde (MDA) was detected by thiobarbituric acid colorimetry, and renal protein expression levels of nephrin, p38 MAPK and p-p38 MAPK were detected by Western blot.Results Compared with the control group, the body weight of the model group was significantly lighter, the levels of 24 h urinary protein, FBG, Scr, BUN, ROS and MDA were significantly increased, and the protein expressions of nephrin, p38 MAPK and p-p38 MAPK were significantly increased, while the activity of SOD was significantly decreased (P < 0.05 and 0.01). Compared with the model group, the body weight of cyclosporine A group significantly increased, the levels of 24 h urinary protein, Scr, BUN, ROS, and MDA were significantly decreased, the expression of nephrin, p38MAPK, and p-p38MAPK protein were significantly decreased, while the activity of SOD were significantly increased in cyclosporine A group (P < 0.05, 0.01).Conclusion Cyclosporine A may inhibit oxidative stress by regulating p38MAPK signaling pathway, improve podocyte injury in renal tissue of DN rats and alleviate the disease progression of DN rats.

R965

西安市衛(wèi)生健康委員會科研一般研究項目（2020yb12）