目的 觀察牛黃中有效成分對大鼠腦缺血再灌注損傷的改善作用，從內(nèi)質(zhì)網(wǎng)應激角度探討其作用機制，并對牛黃有效成分的藥效進行比較研究。方法 SD大鼠隨機分成6組：假手術(shù)組、模型組、清開靈（陽性藥，3 mL/kg）組、牛磺酸（25 mg/kg）組、熊去氧膽酸（UDCA，78 mg/kg）組、?；切苋パ跄懰幔═UDCA，100 mg/kg）組，每組10只。制備大腦中動脈閉塞模型，造成大鼠腦缺血再灌注損傷，采用神經(jīng)功能評分法評定神經(jīng)功能缺損，TTC染色法測定腦梗死體積，免疫組化、Western blotting法檢測缺血腦組織中內(nèi)質(zhì)網(wǎng)應激相關(guān)蛋白（P-PERK、P-EIF2α、ATF4）的表達情況。結(jié)果 與假手術(shù)組比較，模型組大鼠神經(jīng)功能評分顯著降低（P<0.01）；與模型組比較，清開靈組、UDCA組、TUDCA組神經(jīng)功能評分顯著升高（P<0.05、0.01）。與假手術(shù)組比較，模型組大鼠形成明顯缺血灶（P<0.01）；與模型組比較，各給藥組均能明顯減小腦梗死體積（P<0.01）。與假手術(shù)組比較，模型組海馬區(qū)和皮層區(qū)的P-PERK、P-EIF2α、ATF4的表達明顯升高（P<0.01）；與模型組比較，各給藥組均不同程度的減少了P-PERK、P-EIF2α、ATF4的表達，尤以清開靈、TUDCA的下降最明顯。結(jié)論 牛黃有效成分通過抑制內(nèi)質(zhì)網(wǎng)應激改善大鼠腦缺血再灌注損傷，其中TUDCA的作用優(yōu)于?；撬岷蚒DCA。

Objective Using middle cerebral artery occlusion (MCAO) model to observe protective effect of effective components of bezoar on brain damage. To discuss the anti-cerebral ischemia mechanism and compare the efficacy of effective components of bezoar from the endoplasmic reticulum stress intervention angle. Methods Rats were stratified randomly divided into sham group, model group, Qingkailing group (positive drug, 3 mL/kg), taurine group, ursodeoxycholic acid (UDCA, 78 mg/kg) group, taurine-conjugated ursodeoxycholic acid (TUDCA, 100 mg/kg) group. Through establish MCAO model in rats, observed the scores of the neurologic impairment, measured infarct volume by TTC. Immunohistochemistry and Western blotting were Used to detect the content of P-PERK, P-EIF2α, and ATF4. Results Compared with sham group, neurologic impairment scores of model group significantly reduced (P<0.01). Compared with model group, Qingkailing group, UDCA group, and TUDCA group significantly improved neurological function in rats (P<0.05, 0.01). Compared model group, all the treatment groups could significantly reduce the volume of cerebral infarction (P<0.01). Compared with sham group, expression of P-PERK, P-EIF2α, and ATF4 was significantly increased (P<0.01). Compared with model group, all the treatment groups reduced the expression of P-PERK, P-EIF2α, and ATF4 in varying degrees, effect of Qingkailing and TUDCA were more obvious. Conclusion The effective components of bezoar alleviate cerebral ischemia reperfusion injury in rats by inhibiting endoplasmic reticulum stress, the effect of TUDCA is better than that of taurine and UDCA.

教育部博士點新教師基金項目（20130013120005）