目的 应用iTRAQ联合质谱技术筛选COPD大鼠肺组织差异表达蛋白。方法 20只雄性SD大鼠(200~220 g),随机分为对照组和模型组,每组10只,采用熏烟法建立COPD大鼠模型。观察大鼠肺组织病理学改变,测定肺功能,BALF白细胞数,肺组织总蛋白iTRAQ标记后质谱鉴定,用生物信息学方法分析蛋白表达变化。结果 与对照组相比,模型组大鼠支气管黏膜下肌层增厚,肺内可见大量炎性细胞浸润,肺功能降低,BALF白细胞数升高(均P<0.05)。质谱鉴定出4 916种蛋白,筛选出468个差异表达蛋白,其中285个表达上调,183个表达下调。筛选了上皮细胞粘着连接蛋白、fMLP、整合素等与COPD相关蛋白。结论 基于iTRAQ技术的蛋白质组学方法筛选出COPD大鼠差异表达蛋白,为进一步研究COPD的发生机制奠定了基础。

Objective iTRAQ and mass spectrometry were used to screen the differentially expressed proteins in the lung of COPD rats. Methods 20 male SD rats (200-220g)were randomly divided into control group and treatment group, with 10 rats in each group. COPD rat model was established by smoking. The lung function, the number of BALF leukocytes, the total protein iTRAQ in lung tissue were measured and identified by mass spectrometry. The differentially expressed proteins were identified by bioinformatic analysis. Results Compared with the control group, the submucous layer of bronchus in the model group was thickened, a large number of inflammatory cells were seen in the lung, the lung function was reduced, and the number of BALF leukocytes was increased. 4 916 proteins were identified by mass spectrometry, 468 differentially expressed proteins were screened, 285 of which were up-regulated and 183 down regulated. Among them, the important COPD related proteins were epithelial adhesion connexin, fMLP and integrins. Conclusion iTRAQ technology screened out the differentially expressed proteins of COPD rats, which laid the foundation for the further study of COPD mechanism

目的 探讨高脂血症大鼠模型前后血液中氨基酸代谢谱的变化,寻找高脂血症大鼠血液中氨基酸代谢标志物。方法 将SD大鼠随机分为正常对照组、模型组,连续灌胃给药4周后收集大鼠血液,测定各组大鼠血清中TG、TC、HDL-C、LDL-C含量,并运用超高效液相色谱-四极杆-飞行时间质谱(UPLC-Q-TOF-MS/MS)法测定血清中氨基酸代谢谱,利用统计学分析研究不同组动物间的氨基酸代谢的差异。结果 与正常对照组比较,模型组TG、TC、LDL-C含量升高,HDL-C含量降低,高脂血症大鼠模型建模成功;与正常对照组比较,模型组蛋氨酸、苯丙氨酸、脯氨酸、苏氨酸、缬氨酸、甘氨酸等6种氨基酸发生明显改变(P<0.05)。结论 高脂血症大鼠存在氨基酸代谢的紊乱,其中蛋氨酸、苯丙氨酸、脯氨酸、苏氨酸、缬氨酸、甘氨酸等6种氨基酸为其潜在的生物标志物。

Objective To investigate the amino acid metabolism profiles changes in the serum of SD rats, and identify the potential biomarkers. Methods SD rats were divided into normal group and model group. The contents of TG, TC, HDL-C, and LDL-C in the serum of each group were measured, after 4 weeks of continuous intragastric administration. Ultra performance liquid chromatography coupled with electrospray time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS)was used to determine amino acid metabolism profile in serum, and statistical analysis was applied to determine metabolic differences among different groups of rats. Results As compared with normal group, TG, TC, LDL-C were increased and HDL-C was decreased in model group, hyperlipidemia rat model successfully modeled. As compared with normal group, methionine, phenylalanine, proline, threonine, valine, glycine in the amino acid metabolic profiling were decreased in model group (P＜0.05). Conclusion Hyperlipidemia rats have disorders of amino acid metabolism, of which methionine, phenylalanine, proline, threonine, valine, and glycine are potential biomarkers.

目的 分析不同黄芪剂量补阳还五汤治疗大鼠慢性难愈性创面的疗效。方法 选择SPF级健康雄性SD大鼠78只作为本次研究材料,在其背部实施造模创建皮肤缺损性创面,并随机分为不同剂量（15 g、30 g、60 g、120 g）黄芪组,观察并对比各组大鼠创面愈合率及愈合时间。结果 对照组创面愈合率比造模后第3天、7 天、11 天高,差异有统计学意义（P<0.05）;不同剂量黄芪组（排除黄芪组15 g第11天）创面愈合率比模型组高,差异有统计学意义（P<0.05）;第3 d对照组创面愈合率比黄芪组30 g、120 g低,差异有统计学意义（P<0.05）;黄芪15 g组各时间点创面愈合均比黄芪120 g组低,差异有统计学意义（P<0.05）;对照组创面愈合时间较模型组延长,差异有统计学意义（P<0.05）;对照组创面愈合时间较黄芪组延长,差异有统计学意义（P<0.05）;黄芪15 g组创面愈合时间较黄芪组120 g延长,差异有统计学意义（P<0.05）;黄芪30 g、60 g创面愈合时间较黄芪组120 g组延长,差异有统计学意义（P<0.05）。结论 不同黄芪剂量补阳还五汤均具有促进慢性难愈性创面愈合效果,利于缩短创面愈合时间,其中以黄芪30 g、60 g、120 g效果较为显著。

目的 探讨血必净注射液对SAP大鼠TLR4信号通路介导肠黏膜屏障功能障碍的影响。方法 24只SD大鼠随机分成空白组(n=8)、对照组(n=8)和治疗组(n=8)。对照组和治疗组用4.5%牛磺胆酸钠溶液胆胰管逆行注射制备SAP模型,空白组采用等量生理盐水逆行注射。治疗组在造模3 h后经鼠尾静脉注射血必净注射液(3 mL/kg)。三组大鼠造模后观察24 h,然后处死取胰腺和小肠组织送病理检查,采用荧光RT-PCR技术检测TLR4和NF-κB表达水平,采用ELSIA法检测血清TNF-α、IL-6、淀粉酶(AMS)及二胺氧化酶(DAO)水平,比较三组大鼠各项指标。结果 对照组和治疗组小肠组织TLR4和NF-κB表达以及血清TNF-α、IL-6、AMS及DAO水平均高于空白组(P>0.05),治疗组小肠组织TLR4和NF-κB表达以及血清TNF-α、IL-6、AMS及DAO水平低于对照组(P＜0.05)。结论 血必净注射液通过干预SAP大鼠TLR4信号通路,降低小肠组织TLR4和NF-κB的表达,减轻小肠组织的炎症反应,对肠黏膜屏障具有一定的保护作用。

Objective To investigate the effect on intestinal mucosal barrier dysfunction (IBF) of Xuebijing injection mediated by Toll-like receptor 4 (TLR4) signal pathway in rats of severe acute pancreatitis (SAP). Methods 24 Sprague Dawley (SD) rats were randomly divided into Sham group (n=8), control group (n=8) and treatment group (n=8). The SAP model was established by retrograde injection of 4.5% sodium taurocholate into the biliopancreatic duct in control group and treatment group, while control group was injected with the same amount of saline. In treatment group, Xuebijing injection (3 mL/kg) was injected via tail vein after 3h of modeling. All rats were monitored and sacrificed after 24 hours of modeling. Samples of pancreas and intestine were collected for pathologic determination. A fluorescent RT-PCR was used to determine the expression of TLR4 and NF-κB of small intestine. The serum levels of TNF-α, IL-6, amylase (AMS) and diamine oxidase (DAO) were measured by using ELISA. All parameters of three groups were compared. Results The expression of TLR4 and NF-κB of small intestine in control group and treatment group were higher than it in control group (P<0.05), as well as the serum levels of TNF-α, IL-6, AMS and DAO (P<0.05). The expression of TLR4 and NF-κB of small intestine in treatment group were lower than it in control group (P<0.05), as well as the serum levels of TNF-α, IL-6, AMS and DAO (P<0.05). Conclusion Xuebijing injection may not only reduce the expression of TLR4 and NF-κB of small intestine, but also alleviate the inflammation reaction of small intestine by interfering with TLR4 signal pathway, which may have a protective effect on intestinal mucosal barrier in SAP rats.

目的 观察百草枯中毒后大鼠血液中炎症因子的变化,以及大承气汤结合氢化可的松在百草枯中毒治疗中的作用。方法 选用广东省实验动物所的160只SD大鼠,雌雄各半。其中随机抽取 120 只大鼠给予百草枯溶液按18 mg/kg的剂量一次性腹腔注射给药,制造百草枯中毒大鼠模型其余 40只大鼠不作处理,作为正常组。再将模型组分为大承气汤联合氢化可的松组、氢化可的松组及盐水对照组,观察大鼠中毒情况,观察并分析给药后1 d、3 d以及5 d大鼠的肺组织以及血清炎症因子TNF-α、IL-2、IL-6等的变化情况。结果 正常对照组在中毒后1 d、3 d未见大鼠死亡,在5 d有1只动物死亡;模型组大鼠TNF-α、IL-2、IL-6水平高于对照组,差异有统计学意义(P<0.05);正常对照组大鼠各因子水平,随着中毒时间的延长逐渐增加,均有差异(P<0.05);大承气汤联合氢化可的松组给药后各时间点TNF-α、IL-2、IL-6降低,与氢化可的松组、盐水对照组均有差异(P<0.05)。结论 大鼠百草枯中毒后,肺组织发生纤维化改变,且TNF-α、IL-2、IL-6因子的水平升高,随着时间的推移,呈现上升趋势;大承气汤对百草枯中毒大鼠肺组织具有保护作用,可能调控各炎症因子作用,减缓病情进展来实现。

目的 探讨自体心包膜组织对急性心肌梗死大鼠心脏功能的影响。方法 筛选合格的模型动物随机分为三组:心包去除组:仅去除心包膜;心梗组:前降支结扎法建立大鼠心肌梗死模型3周后仅开胸;移植组:前降支结扎法建立大鼠心肌梗死模型,3周后将心包膜移植于心肌梗死及周边区。实验4周后,通过心动图评价实验动物心脏功能,使用Masson染色检测动物心肌梗死大小,通过免疫荧光评价动物心肌存活率、观察血管新生状况,Western blot检测Caspase-3蛋白/Bcl-2基因表达情况。结果 4周后,心包去除组大鼠的心电图监测结果未见有室性颤动;而心梗组、心梗+移植组均有非致死性室性颤动。相比心梗组,心梗+移植组改善了心功能,降低了心肌凋亡指数,免疫Bcl-2蛋白表达升高,而Caspase-3蛋白表达降低。结论 提示自体心包膜移植不会导致恶性室性心律失常,相对有较高的安全性;并能促进心肌梗死细胞恢复心功能,其改善机制可能与通过修补心室重构途径同时抑制缺血区域细胞凋亡有关。

Objective To explore the effect of autologous pericardial transplantation for treating the myocardial infarction (MI) in experimental rats. Methods 30 SD rats were randomly divided in to three equal parts: Pericardial removal group (PR group): only pericardium tissue was removed; Myocardial infarction group (MI group): the anterior descending branch ligation method established a rat model of myocardial infarction and only opened the chest after 3 weeks. Autologous pericardium transplantation (APT group): After established the MI model of SD rats, 3 weeks later, the autologous pericardial patch was harvested and transplanted to infarcted zone. Four weeks after the surgery, the cardiac function and serum biochemistry were analyzed for all the experimental rats. The cardiac function was evaluated by echocardiography, which the size of the infarction were examined by Masson staining, the survival time of transplanted autologous pericardial and angiogenesis were measured by immunohistochemistry, the protein expressions of Caspase and the gene expressions of Bcl were examined by Western blot analysis. Results 4 week after the 2^nd operation, no ventricular fibrillation was detected in the ECG of PR group. Fatal ventricular fibrillation wasn't detected in the ECG of MI group and APT group. Compared with MI group, APT group improved cardiac function and decreased myocardial apoptosis index(P<0.05),which similar to PR group. APT group has the higher density of angiogenesis at infracted area to MI group but less than that of PR group. PT group had decreased protein expressions of Caspase-3 and the expressions of Bcl-2 were decreased. Conclusion Autologous pericardial transplantation could recover myocardial infarction cells, which will improve the cardiac function in experimental rats with MI.

目的 探讨胆碱能受体激动剂尼古丁对子痫前期大鼠的治疗作用及机制。方法 将30只妊娠SD大鼠分为对照组（n =10）、子痫前期组（n =10）和尼古丁治疗组（n =10）。子痫前期组中,大鼠妊娠第14天注射内毒素（l.0 μg/kg）;对照组给予等量生理盐水2 mL,研究组妊娠第14 天开始皮下注射尼古丁1 mg/（kg·d）至妊娠第19天。检测各组干预前后收缩压、24小时蛋白、妊娠结局和大鼠外周血IL-6,TNF-α,IFN-γ和IL-1β的表达水平。结果 和对照组相比,大鼠动脉收缩压妊娠第14天注射LPS后升高,治疗组中在尼古丁注射后,妊娠第16天、第18天较子痫前期组血压下降（14.99±0.48 vs 16.61±0.55 kPa,15.01±0.60 vs 17.04±0.49 kPa,P<0.05）;大鼠24 h蛋白尿在子痫前期组中妊娠第17、19天升高（P<0.05）,尼古丁治疗组尿蛋白较子痫前期组降低（P <0.05）。妊娠第20天,子痫前期组胎儿重量和对照组相比下降（P <0.05）,尼古丁治疗组较子痫前期模型组胎儿重量增加（P <0.05）。各组间存活胎儿数、胎盘重量差异无统计学意义（P >0.05）。子痫前期组炎性因子IL-6,TNF-α,IFN-γ和IL-1β 较对照组升高,差异有统计学意义;尼古丁治疗组IL-6,TNF-α,IFN-γ 和IL-1β 降低（P <0.05）。结论 胆碱能受体激动剂尼古丁通过降低炎性反应来改善子痫前期大鼠的妊娠结局。

Objective To examine the effects and mechanism of cholinergic receptor agonist nicotine on preeclampsia rats. Methods 30 pregnant SD rats were divided into control group（n=10）,preeclampsia group（n=10） and nicotine treatment group（n=10）.In preeclampsia group,rats were injected LPS（l.0 μg/kg） on the day 14th of gestation,the control rats were injected 2 mL of physical saline on the day 14th of gestation,the rats in nicotine treatment group were injected nicotine 1mg/（kg·d） from the day 14th to the day 19th of gestation. The systolic blood pressure,24 hour urine protein,pregnancy outcome and serum levels of IL-6,TNF-α,IFN-γ and IL-1β were compared between each groups. Results Compared to control group,the systolic blood pressure rose after LPS injection on the day 14th of gestation,the systolic blood pressure in nicotine treatment group decreased on the day 16th and the day 18th of gestation compared to preeclampsia group（14.99±0.48 vs 16.61±0.55 kPa,15.01±0.60 vs 17.04±0.49 kPa,P<0.05）.The 24 hour urine in preeclampsia group rose on day 17 and day 19 of gestation（P <0.05）,which decreased in nicotine group（P <0.05）. The fetal weight were higher in nicotine treatment group compared to the preeclampsia group,there were no statisitical difference in viable fetal number and placental weight among groups. The serum levels of IL-6,TNF-α,IFN-γ IL-1β were higher in preeclampsia group compared to the control group,while nicotine decreased the levels of IL-6,TNF-α,IFN-γ IL-1β（P <0.05）. Conclusion Nicotine improved pregnancy outcome of LPS induced preeclampsia rats by decreasing inflammatory levels.

目的 评价鞘内注射雷帕霉素对CCI神经病理性痛大鼠的痛阈及脊髓背角胶质细胞表达的影响。方法 健康雄性SD大鼠30只随机分为6组:①CCI组:CCI术后14天处死;②正常对照组:不做任何处理; ③前对照剂组:鞘内置管3天后行CCI术,术后4小时后鞘内给同体积生理盐水,连给3天; ④前给药组:鞘内置管3天后行CCI术,术后4小时鞘内给雷帕霉素溶液,连给3天; ⑤后对照剂组:鞘内置管3天后行CCI术,术后7天鞘内给同体积生理盐水,连给3天;⑥后给药组:鞘内置管3天后行CCI术,术后7天鞘内给雷帕霉素溶液,连给3天。各组于CCI术前1天和术后第2、4、6、8、10、12、14天测机械痛阈和热痛阈。术后14天测痛后用多聚甲醛灌注大鼠,取L4~5脊髓,免疫组化染色,星形胶质细胞标记蛋白(GFAP)检测星形胶质细胞表达变化,并定量分析。结果 与对照组相比,CCI手术组热痛阈和机械痛阈从CCI手术后第4天开始下降(P<0.05);前后给药对照剂组与CCI组相比,差别无统计学意义(P>0.05)。前给药组痛阈从CCI手术后第4天开始上升并持续至手术后第14天,与CCI组相比,差别有统计学意义 (P<0.05)。与CCI组相比,后给药组痛阈从CCI第8天开始上升并持续至手术后第14天,差别有统计学意义(P<0.05)。 与正常对照组比较,CCI组、前、后对照剂组手术侧脊髓背角GFAP染色阳性区平均光密度与阳性面积均有增加,差别有统计学意义(P<0.05)。前、后给药组手术侧GFAP染色阳性区平均光密度与阳性面积与CCI组比较,均有明显降低,差别有统计学意义(P<0.05)。结论 鞘内注射雷帕霉素可缓解大鼠神经病理性痛,并抑制脊髓背角胶质细胞的激活。

Objective To evaluate the effects of intrathecal injection of rapamycin on pain threshold and spinal cord gliacyte activation in rats of neuropathic pain. Methods Healthy 30 male SD rats were randomly divided into 6 groups(n=5 in each group): ① control group without operation or intrathecal injection. ②CCI group without intrathecal injection. ③ intrathecal injection of rapamycin 10 μg(10 μL) 4 hours after CCI operation and the next 2 days once a day. ④ intrathecal injection of NS10 μL 4 hours after CCI operation and the next 2 days once a day. ⑤ intrathecal injection of rapamycin 10 μg(10 μL) 7 days after CCI operation and the next 2 days once a day.⑥ intrathecal injection of NS10 μL 7 days after CCI operation and the next 2 days once a day. Mechanical and thermal threshold were tested 1 day before the CCI operation and 2^th、4^th、6^th、8^th、10^th、12^th、14^th days after the CCI operation for all the rats. Lumbar segment of spinal cords was removed for determination of glial fibrillary acidic protein(GEAP) in spinal cord by immuohistochemistry dyeing and assay in the 14th day after CCI operation for all the rats. Results Mechanical and thermal hyperalgesia emerged on 4th day and maintained till 14th day after CCI operation(P<0.05). After intrathecal injection of rapamycin 4 hours or 7days after CCI, mechanical and thermal threshold significantly increased compared to intrathecal injection of NS(P<0.05). And the sum area of GFAP positive and the mean density of GFAP positive area in the dorsal horn of operation side greatly increased in rapamycin treated groups compared NS treated groups(P<0.05). Conclusion Intrathecal injection of rapamycin may attenuate CCI induced hyperalgesia and inhibit the activation of astrocyte.

目的 探索锌剂治疗大鼠慢性细菌性前列腺炎(CBP)的机理及影响。方法 健康成年雄性大鼠100只,随机分为正常对照组(n=20)、CBP模型对照组(n=20)、CBP锌剂治疗组(n=20)、CBP左氧氟沙星治疗组(n=20)及CBP锌剂与左氧氟沙星混合治疗组(n=20)。采用消痔灵及大肠埃希菌制备CBP大鼠模型。CBP锌剂治疗组、CBP左氧氟沙星治疗组及CBP混合治疗组给予相应药物灌胃治疗,正常对照组及CBP模型对照组给予无菌生理盐水灌胃。疗程10 d,分别于2 d、4 d、6 d、8 d、11 d取各组大鼠前列腺,检测细菌数量并分离鉴定细菌性质。于4 d、9 d、14 d、20 d、28 d取各组大鼠前列腺,进行组织病理学检测。结果 CBP各治疗组大鼠前列腺组织的细菌数量与模型对照组相比均明显降低(P﹤0.05)。CBP混合治疗组大鼠前列腺内细菌在治疗8 d后不能检出。4～6 d CBP混合治疗组大鼠前列腺组织的细菌数量与CBP锌剂治疗组相比明显降低(P﹤0.05)。正常对照组大鼠前列腺病理学检查未见明显病理变化;模型对照组大鼠前列腺组织表现为慢性炎症的病理变化;各治疗组大鼠前列腺慢性炎症改变均有不同程度缓解,其中混合治疗组的慢性炎症明显减轻。结论 锌剂具有活化提高前列腺组织细胞抗菌能力的作用,有利于前列腺组织炎性病理损害的缓解以及损伤组织的修复,与敏感抗生素结合治疗CBP具有更显著的治疗效果。

Objective To explore the zinc agent in the treatment of chronic bacterial prostatitis (CBP) rats and the effect. Methods 100 healthy adult male rats, were randomly divided into normal control group (n=20), CBP model group (n=20), CBP zinc treatment group (n=20), CBP levofloxacin treatment group (n=20) and mixed treatment group of CBP zinc and levofloxacin (n=20). Preparation of the CBP rat model was made by Xiaozhiling and E.coli system. CBP zinc treatment group, CBP levofloxacin treatment group and CBP mixed treatment group were given the appropriate drugs for treatment,besides,the normal control group, CBP model control group were given sterile saline. It took 10d. Rats in each group at 2d, 4d, 6d, 8d, 11d were detected, including the number of bacteria and the bacteria isolation and identification properties. The pathological study in 4d, 9d, 14d, 20d, 28d and prostate of rats in each group were detected. Results The prostate tissue of the CBP group rats in the treatment of bacterial number compared with the model control group decreased significantly (P<0.05). CBP mixed treatment of prostate were not detected in bacteria after 8d treatment.4 - 6 days of CBP treatment of prostate tissue in rats of the treatment group compared with the quantity of bacteria and CBP zinc decreased significantly (P<0.05). Normal control group rats pathological prostate pathology examination showed no significant pathological prostate tissue; The model control group rats showed chronic inflammatory pathological changes; The treatment group rat prostate inflammatory changes were alleviated chronic inflammation, which mixed treatment group were significantly reduced. Conclusion Zinc enhances prostate tissue antibacterial ability, is conducive to the inflammation in prostate tissue response and the repair of damaged tissue. Sensitive antibiotics combined with treatment of CBP have a significant therapeutic effect.

目的 探讨川芎嗪对链脲佐菌素(STZ)诱导2型糖尿病大鼠肾病的治疗作用及机制。方法 SD大鼠50只,随机分为正常组和模型组。除正常组外,其余大鼠均给予高脂-高糖饲料喂养4周,再给予链脲佐菌素(40 mg/kg,ip),72 h后测定空腹血糖,将血糖值高于16.67 mmol/L的大鼠随机分成4个组即模型组,二甲双胍阳性组(250 mg/kg),川芎嗪低、高剂量组(80、160 mg/kg),连续给予相应试药8周。其中正常组和模型组的大鼠均给予同等量蒸馏水灌胃。实验结束时,测定大鼠血糖、尿蛋白、血尿素氮和血肌酐含量;免疫组化法测定大鼠肾组织TLR4和caspase3蛋白表达。光镜下观察肾脏病理学变化。结果 与模型组比较,二甲双胍组和川芎嗪高剂量组给药8周后,大鼠动态空腹血糖均能明显降低(P<0.05),大鼠动态尿蛋白显著性降低(P<0.01,P<0.05); 二甲双胍和高剂量组TLR4和caspase3蛋白表达明显低于模型组(P<0.05);肾脏组织病理性损伤明显减轻。结论 川芎嗪对STZ诱导2型糖尿病大鼠肾病具有保护作用,其机制可能与下调TLR4表达作用有关。

Objective To investigate the therapeutic effects and mechanisms of tetramethylpyrazine (TMP) on streptozocin(STZ)-induced-nephropathy in type 2 diabetic rats. Methods 50 SD rats were randomly divided into normal group(n=10) and model group(n=40). The model rats were fed on high fat and sugar diets for 4 weeks, then given STZ(40 mg/kg,ip). After 72 hours, the fasting blood glucose (FBG) was measured. Rats with high FBG above 16.67mmol/L were randomly divided into four groups: model, metformin(Met, 250 mg/kg)and TMP (80 mg/kg, 160 mg/kg) groups for treating 8 weeks, and both the control and model groups were given equals distilled water by intragastric administration. At the end of the experiment, blood glucose, urine protein, blood urea nitrogen and creatinine were measured. The expression of TLR4 and caspase3 protein in kidney tissue of rats was determined by immunohistochemistry. Pathological changes of kidney were observed under light microscope. Results Compared with the model group, metformin and high dose of TMP administered after 8 weeks, rats can significantly reduce the dynamic fasting blood glucose(P<0.05). Urinary protein excretion of total dynamic decreased significantly (P<0.01, P<0.05); the protein expression of TLR4 and caspase3 in the metformin group and high dose group was significantly lower than that in the model group (P<0.05); kidney tissue pathological damage was significantly reduced. Conclusion TMP has a protective effect on STZ induced nephropathy in type 2 diabetic rats, and its mechanism may be related to the down-regulation of TLR4 expression.