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目的探讨通络保肾复方及其拆方对链脲佐菌素(STZ)诱导糖尿病大鼠高血糖肾损伤内质网应激反应(ERS)启动因子P-IRE1α和分子伴侣GRP78的影响。方法将雄性SD大鼠随机分成正常组和造模组。造模组大鼠采用腹腔注射STZ方法建立糖尿病大鼠模型。造模成功后将造模组大鼠随机分成模型对照组、缬沙坦组(8.93 mg/kg)、通络保肾复方组(19.43 g/kg)、通络保肾补虚组(6.92 g/kg)、通络保肾解毒组(12.5 g/kg)。观察各组大鼠日常活动的一般情况;应用免疫组化法及IPP软件半定量分析6周和16周各组大鼠p-IRE1α及GRP78的蛋白表达。结果普通光镜下可见P-IRE1α、GRP78主要位于造模组大鼠肾脏近段、远端肾小管细胞及肾小球细胞的胞浆内;IPP免疫组化半定量法显示:6周和16周模型组与正常组大鼠相比较P-IRE1α、GRP78的蛋白表达增加(P<0.05);与模型组大鼠相比,6周和16周缬沙坦组、通络保肾复方组、通络保肾补虚组、通络保肾解毒组P-IRE1α、GRP78的蛋白表达减少(P<0.05),各治疗组之间无差别(P>0.05)。结论糖尿病高血糖诱导肾损伤大鼠模型中存在内质网应激反应的激活;通络保肾复方及其拆方均可能通过抑制内质网应激而发挥肾脏保护作用;同时可推测糖尿病高血糖肾损伤的中医学核心病机是本虚标实。
Objective To investigate the effect of Tonglu Baoshen Compound and its decomposed formulas on endoplasmic reticulum stress response (ERS) promoter P-IRE1α and molecular chaperone GRP78 in streptozotocin-induced diabetic rats with hyperglycemia and renal injury. Methods Male SD rats were randomly divided into normal group and model group. Rats in model group were induced by intraperitoneal injection of STZ to establish diabetic rat model. The model rats were randomly divided into model control group, valsartan group (8.93 mg / kg), Tongluolianjin group (19.43g / kg), Tonglunshen tonic group (6.92 g / kg), Tongluo detoxification group (12.5 g / kg). The general situation of daily activities of rats in each group was observed. The protein expression of p-IRE1α and GRP78 in rats of each group were semi-quantitatively analyzed by immunohistochemistry and IPP software. Results The expression of P-IRE1α and GRP78 were mainly found in the proximal renal proximal tubules, distal tubule cells and glomerular cytoplasm of rats in model group. IPP immunohistochemical semi-quantitative analysis showed that the expression of P-IRE1α Compared with the model group, the expression of P-IRE1α and GRP78 protein increased in the model group compared with the model group at 6 and 16 weeks (P <0.05) There was no significant difference in the expression of P-IRE1α and GRP78 (P <0.05) between Tonglu Huatang tonic group and Tonglintu shenshen detoxification group (P> 0.05). Conclusions Endoplasmic reticulum stress response is activated in diabetic rat model induced by hyperglycemia. Tongluoluxin Decoction and its disassembled prescription may play a protective role in kidney by inhibiting the endoplasmic reticulum stress. Blood sugar kidney injury in the core pathogenesis of this virtual reality.