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目的观察亚甲蓝(MB)对百草枯(PQ)中毒大鼠肾和空肠损伤的保护作用,并探讨其可能机制。方法雄性SD大鼠分为6组(n=6):正常对照组(0.2 m L 0.9%生理盐水,ip)、MB组(MB 2 mg?kg~(-1),ip)、PQ模型组(PQ 35 mg?kg~(-1),ip)、PQ+MB ig治疗组(PQ 35 mg?kg~(-1),ip;MB 2 mg?kg~(-1),ig)、PQ+MB ip治疗组(PQ 35 mg?kg~(-1),ip;MB 2 mg?kg~(-1),ip)和PQ+MB 2 h ip治疗组(PQ 35 mg?kg~(-1),ip,2 h后+MB 2 mg?kg~(-1),ip);48 h后,取肾和空肠组织,进行HE染色及病理损伤评分;检测血尿素氮(BUN)含量、血肌酐(Cr)含量、超氧化物歧化酶(SOD)活性、髓过氧化物酶(MPO)活性、三磷酸腺苷(ATP)含量和丙二醛(MDA)含量;末端脱氧核苷酸转移酶介导d UTP缺口末端标记(TUNEL)法检测凋亡情况;免疫组化法检测肾组织中血红素加氧酶-1(HO-1)蛋白含量。结果与正常对照组和MB组相比,PQ组大鼠肾和空肠组织的病理损伤评分增高(P<0.05),BUN和Cr含量增加(P<0.05),SOD活性和ATP含量降低(P<0.05,P<0.01),MPO活性和MDA含量增加(P<0.05),大鼠肾和空肠组织凋亡率增高(P<0.01);与PQ组相比,所有MB治疗组大鼠肾和空肠组织病理损伤评分降低(P<0.05),BUN和Cr含量减少(P<0.05),SOD活性和ATP含量增高(P<0.05,P<0.01),MPO活性和MDA含量降低(P<0.05),大鼠肾和空肠组织凋亡率降低(P<0.05),肾组织HO-1免疫组化评分增高(P<0.05)。结论 MB能减轻PQ中毒大鼠的肾和空肠损伤,其保护机制可能与MB可提高HO-1表达有关。
Objective To observe the protective effect of methylene blue (MB) on renal and jejunal injury induced by paraquat (PQ) in rats and its possible mechanism. Methods Male SD rats were divided into 6 groups (n = 6): normal control group (0.2 m L 0.9% saline, ip), MB group (MB 2 mg? Kg -1, ip) (PQ 35 mg? Kg -1, ip), PQ + MB ig treatment group (PQ 35 mg? Kg -1, ip; MB 2 mg? Kg -1), PQ (PQ 35 mg? Kg ~ (-1), ip; MB 2 mg? Kg ~ (-1), ip) and PQ + MB 2 h ip group 1), ip, 2 mg? Kg ~ (-1) after 2 h, ip); After 48 h, the kidneys and jejunum tissues were taken for HE staining and pathological damage score; Blood urea nitrogen (BUN) Serum creatinine (Cr), superoxide dismutase (SOD) activity, myeloperoxidase (MPO) activity, ATP content and malondialdehyde (MDA) d UTP nick end labeling (TUNEL) method was used to detect apoptosis; immunohistochemistry was used to detect the content of heme oxygenase-1 (HO-1) in renal tissue. Results Compared with normal control group and MB group, the pathological damage scores of kidney and jejunum in PQ group were significantly increased (P <0.05), the content of BUN and Cr increased (P <0.05) and the activity of SOD and the content of ATP decreased (P < 0.05, P <0.01). The MPO activity and MDA content increased (P <0.05), and the apoptosis rate in kidney and jejunum increased (P <0.01). Compared with PQ group, The levels of BUN and Cr decreased (P <0.05), the activities of SOD and ATP increased (P <0.05, P <0.01), the activities of MPO and MDA decreased (P <0.05) The apoptosis rate of kidney and jejunum in rats decreased (P <0.05), and the immunohistochemical score of HO-1 in kidney increased (P <0.05). Conclusion MB can alleviate the injury of kidney and jejunum in rats with PQ poisoning. The protective mechanism may be related to the increase of HO-1 expression by MB.