葛根素注射液对蛛网膜下腔出血大鼠脑水肿及cAMP/PKA/AQP4通路的影响
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R743.35

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Puerarin Injection Has Effect on Brain Edema and cAMP/PKA/AQP4 Pathway in Rats with Subarachnoid Hemorrhage
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    摘要:

    目的:研究葛根素注射液对蛛网膜下腔出血(SAH) 模型大鼠环腺苷酸(cAMP) /蛋白激酶A(PKA) /水通道蛋白4(AQP4) 通路和脑部积水的影响。方法:将78 只雄性SD 大鼠分为假手术组、模型组、葛根素注射液低、中、高剂量组(低、中、高剂量组) 和阳性药组。除假手术组外,向其余各组大鼠枕大池注射股动脉血2次进行沉积,构建大鼠SAH模型,模型制备成功后假手术组和模型组腹腔注射生理盐水2 mL,低、中、高剂量组分别按50、100、200 mg/(kg·d)的剂量注射葛根素注射液,阳性药组按0.5 mg/(kg·d)的剂量注射地塞米松磷酸钠注射液。对大鼠进行神经功能评分、测定脑含水量、Elisa 检测脑脊液中cAMP与PKA水平、RT-PCR与Western blot检测脑组织中PKA与AQP4 mRNA及蛋白水平。结果:与假手术组比较,模型组神经功能评分、脑含水量、脑脊液cAMP 与PKA 含量、脑组织PKA 与AQP4 mRNA 与蛋白水平均显著升高(P<0.05)。与模型组比较,阳性药组、中、高剂量组神经功能评分、脑含水量、脑脊液cAMP与PKA含量、脑组织PKA与AQP4 mRNA及蛋白水平,低剂量组脑含水量、脑组织中PKA与AQP4 mRNA及蛋白水平均显著降低(P<0.05)。与阳性药组比较,低、中剂量组神经功能评分、脑脊液cAMP与PKA含量、脑组织AQP4 mRNA及蛋白水平,低剂量组脑含水量、PKA mRNA及蛋白水平均显著升高(P<0.05)。与低剂量组比较, 中、高剂量组神经功能评分, 高剂量组脑含水量、脑脊液PKA 含量、脑组织PKA 与AQP4mRNA 及蛋白水平均显著降低(P<0.05)。与中剂量组比较,高剂量组神经功能评分、脑组织中AQP4 蛋白水平均显著降低(P<0.05)。结论:葛根素可能通过调节cAMP/PKA/AQP4 通路,降低AQP4 的水通道作用,从而减少蛛网膜下腔积水,缓解SAH。

    Abstract:

    Abstract:Objective:To study the effect of puerarin injection on cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)/aquaporin 4(AQP4) pathway and brain edema in model rats with subarachnoid hemorrhage(SAH). Methods:A total of 78 male SD rats were divided into the sham operation group,the model group,the puerarin injection groups of low-dose,medium-dose and high-dose respectively(the low-dose,medium-dose and high-dose groups) and the positive medicine group. Except for the sham operation group, the other groups were given injections of femoral arterial blood into cisterna magna for deposition twice. After building the SAH model of rats,the sham operation group and the model group were given intraperitoneal injection of 2 mL saline; the low- dose, medium- dose and high- dose groups were respectively given puerarin injection according to the dose of 50,100,200 mg/(kg·d);the positive medicine group was given dexamethasone sodium phosphate injection according to the dose of 0.5 mg/(kg·d). The nerve function was scored;the brain water content was measured;the levels of cAMP and PKA in cerebrospinal fluid were detected by Elisa;the levels of mRNA and protein in PKA and AQP4 in brain tissue were detected by RT- PCR and Western blot. Results: Compared with those in the sham operation group,the score of nerve function,the brain water content,the contents of cAMP and PKA in cerebrospinal fluid and the levels of mRNA and protein in PKA and AQP4 in brain tissue in the model group were significantly increased(P<0.05).Compared with those in the model group,the scores of nerve function,the brain water content,the contents of cAMP and PKA in cerebrospinal fluid and the levels of mRNA and protein in PKA and AQP4 in brain tissue in the positive medicine group,the medium-dose group and high-dose group,as well as the brain water content and the levels of mRNA and protein in PKA and AQP4 in brain tissue in the low-dose group were significantly decreased(P<0.05). Compared with those in the positive medicine group,the scores of nerve function,the contents of cAMP and PKA in cerebrospinal fluid and the levels of mRNA and protein in AQP4 in brain tissue in the medium-dose and high-dose groups,as well as the brain water content and the levels of mRNA and protein in PKA in brain tissue in the low-dose group were significantly increased(P<0.05). Compared with those in the low-dose group,the scores of nerve function in the medium-dose and high-dose groups,as well as the brain water content,PKA content in cerebrospinal fluid,the levels of mRNA and protein in PKA and AQP4 in brain tissue in the high-dose group were significantly decreased(P<0.05). Compared with those in the medium-dose group,the score of nerve function and the level of protein in AQP4 in brain tissue in the high-dose group were significantly decreased(P < 0.05).Conclusion: By regulating the cAMP/PKA/AQP4 pathway, puerarin can reduce the effect of AQP4 to reduce the subarachnoid hydrops and alleviate SAH.

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应勇,柳慧金.葛根素注射液对蛛网膜下腔出血大鼠脑水肿及cAMP/PKA/AQP4通路的影响[J].新中医,2020,52(11):1-5

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  • 在线发布日期: 2020-06-04
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