目的 探究安腦丸聯(lián)合丙戊酸鈉對(duì)老年躁狂抑郁癥的臨床效果及對(duì)患者糖原合成酶激酶3（GSK3）活性、炎癥狀態(tài)、認(rèn)知功能的影響。方法 前瞻性選取焦作市第四人民醫(yī)院2018年2月-2020年9月收治的老年躁狂抑郁癥患者92例作為研究對(duì)象，按照隨機(jī)數(shù)字表法分為對(duì)照組和試驗(yàn)組，每組各46例。對(duì)照組服用丙戊酸鈉緩釋片治療，初始劑量為每次500 mg，每天1次；1周內(nèi)可根據(jù)患者病情、耐受情況增加至每天1 000~1 500 mg。試驗(yàn)組在對(duì)照組基礎(chǔ)上加用安腦丸，初始劑量為每次6 g，每天2次；2周后調(diào)整藥物劑量為每次3 g，每天1次。兩組藥物均為口服，均持續(xù)治療8周。比較兩組治療總有效率，分別于治療前及治療8周后采用貝克-拉范森躁狂量表（BRMS）及漢密爾頓抑郁量表（HAMD）評(píng)價(jià)兩組患者的躁狂癥狀和抑郁癥狀，檢測(cè)兩組患者外周血單個(gè)核細(xì)胞（PBMC）中GSK3相關(guān)蛋白及血清炎癥因子腫瘤壞死因子-α（TNF-α）、白細(xì)胞介素-1（IL-1）、白細(xì)胞介素-10（IL-10）等水平，采用元認(rèn)知問卷（MCQ-30）評(píng)分評(píng)估患者認(rèn)知功能，觀察并記錄兩組患者不良反應(yīng)發(fā)生情況。結(jié)果 治療8周后，試驗(yàn)組總有效率為93.48%，顯著高于對(duì)照組的78.26%（P<0.05）。治療8周后兩組BRMS、HAMD評(píng)分較治療前下降（P<0.05），試驗(yàn)組低于對(duì)照組（P<0.05）；治療8周后兩組PBMC中pSer21-GSK3α、pSer9-GSK3β、total-GSK3α、total-GSK3β、血清IL-10水平較治療前升高（P<0.05），試驗(yàn)組高于對(duì)照組，血清TNF-α、IL-1水平低于治療前（P<0.05），試驗(yàn)組低于對(duì)照組（P<0.05）；治療8周后兩組MCQ-30量表認(rèn)知自信、自我認(rèn)知意識(shí)、積極信念、控制思維的傾向、失控和危機(jī)感評(píng)分較治療前升高（P<0.05），試驗(yàn)組高于對(duì)照組（P<0.05）；試驗(yàn)組不良反應(yīng)發(fā)生率與對(duì)照組比較無明顯差異（P>0.05）。結(jié)論 安腦丸聯(lián)合丙戊酸鈉治療老年躁狂抑郁癥能顯著提高療效，減輕患者躁狂與抑郁程度，還可下調(diào)GSK3活性、炎癥因子表達(dá)水平，改善認(rèn)知能力，且不增加藥物不良反應(yīng)。

Objective To explore the clinical effect of Annao Pill combined with sodium valproate in the treatment of senile manic depression and its effect on glycogen synthase kinase 3 (GSK3) activity, inflammatory state and cognitive function. Methods A total of 92 elderly patients with manic depression treated in Jiaozuo Fourth People's Hospital from February 2018 to September 2020 were prospectively selected as the research objects. They were randomly divided into control group and experimental group, with 46 cases in each group. Patients in the control group were treated with Sodium Valproate Sustained-Release Tablets, with an initial dose of 500 mg once a day, within one week, it can be increased to 1 000—1 500 mg per day according to the patient's condition and tolerance. On the basis of the control group, patients in the experimental group were added with Annao Pill, with an initial dose of six g each time, twice a day, after two weeks, the dosage was adjusted to three g each time, one time a day. Both groups were treatedorally for eight weeks. The total effective rates of the two groups were compared. The manic symptoms and depressive symptoms of the two groups were evaluated by Bech-Rafaelsen Mania Rating Scale (BRMS) and Hamilton Depression Scale (HAMD) before and eight weeks after treatment. The levels of the GSK3 related protein in peripheral blood mononuclear cells (PBMC) and serum inflammatory factor tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interleukin-10 (IL-10) were detected. Cognitive function were evaluated by Metacognitive questionnaire (MCQ-30), and the adverse reactions of the two groups were observed and recorded. Results After eight weeks of treatment, the total effective rate in the experimental group was 93.48%, which was significantly higher than 78.26% in the control group (P < 0.05). After eight weeks of treatment, the scores of BRMS and HAMD in the two groups decreased compared with those before treatment (P < 0.05), and the scores in the experimental group were lower than those in the control group (P < 0.05). The levels of pSer21-GSK3α, pSer9-GSK3β, total-GSK3α, total-GSK3β in PBMC and serum IL-10 of the two groups after eight weeks of treatment were higher than those before treatment (P < 0.05), and the levels in the experimental group were higher than those in the control group (P < 0.05). The level of serum TNF-α and IL-1 of the two groups after eight weeks of treatment were lower than that those before treatment (P < 0.05), and the levels in the experimental group were lower than those in the control group (P < 0.05). After eight weeks of treatment, the scores of MCQ-30 scale cognitive selfconfidence, self-awareness, positive belief, tendency to control thinking, out of control and sense of crisis in the two groups were higher than those before treatment (P < 0.05), and those in the experimental group were higher than those in the control group (P < 0.05). There was no significant difference in the incidence of adverse reactions between the experimental group and the control group (P>0.05). Conclusion The combination of Annao Pill and sodium valproate in the treatment of senile manic depression can significantly improve the curative effect, reduce the degree of mania and depression, reduce the activity of GSK3 and the expression level of inflammatory factors, improve cognitive ability, and do not increase adverse drug reactions.

R971