Objective:To observe the effect of Tongluoyishen Prescription drug containing serum on cultured in high glucose of rat glomerular mesangial cells(MC)proliferation and GRP78、Caspase - 12 mRNA expression, discussing the effect and mechanism of Tongluoyishen Prescription for protecting kidney from the endoplasmic reticulum stress. Methods:The cultured MC were randomly divided into 6 groups: Normal group, model group, Tongluoyishen high dose group、Middle dose、low dose group and and Western medicine group. After cultured for 12 h, 24 h, 48 h and 72 h, MC proliferation were detected by MTT, The expression of GRP78 and Caspase - 12 were detected by RT - PCR method. Results:(1)Compared with normal group, the model group proliferation were sig-nificantly increased in all time points (P < 0. 05 or P < 0. 01); Compared with the model group, MC proliferation were significantly decreased in three Chinese medicine groups at 24 h, 48 h and 72 h (all P < 0. 01), and the large dose group was the best (P <0. 01). MC proliferation in western medicine group were lower than those of high dose group at 12 h, 24 h (all P < 0. 05), and there were no significant difference between the two groups at 48 h, 72 h (P > 0. 05). (2)Compared with normal group, the model group MC GRP78 mRNA is sustained increase at 24 h and 48 h, but significantly decreased at 72 h (P < 0. 05, P < 0. 01); GRP78 mRNA expression among four drug groups: Western medicine group > small dose group > middle dose group > high dose group at 48 h, West-ern medicine group > small dose group > high dose group at 72 h (all P < 0. 05, P < 0. 01). At the same time, the expression of GRP78 mRNA showed a trend of increasing from 24 h to 48 h and 72 h. It is indicated that the drugs can delay the increase of GRP78 and delay the ERS to continue play its protective role. (3)Compared with normal group, the model group MC Caspase - 12 mRNA is significantly increased at 48 h、72 h (P < 0. 01). Compared with the model group, Caspase - 12 mRNA expression were significantly decreased in the four drug groups at 48 h and 72 h (P < 0. 05 or P < 0. 01). Caspase - 12 mRNA expression of the three Chinese medicine groups was significantly lower than that of the western medicine group at 48 h (P < 0. 05). Caspase - 12 mRNA expression among the three Chinese medicine groups: small dose group > middle dose group > high dose group at 72 h (P < 0. 01 or P < 0. 05). The casspase - 12 mRNA expression was negatively correlated with the dosage. Conclusion:Endoplasmic reticulum stress were signifi-cantly when MC cultured in high glucose; Tongluo Yishen Prescription can significantly inhibit MC proliferation. It is speculated that the mechanism is related to delay GRP78 growth and down regulated Caspase - 12 mRNA expression.%目的：观察通络益肾方含药血清对高糖培养下大鼠系膜细胞(MC)增殖及 GRP78、Caspase -12 mRNA 表达的影响，从内质网应激角度探讨该方的肾保护机制。方法：肾小球 MC 随机分为6组：正常组、模型组、通络益肾方大、中、小剂量组及西药组，分别培养12 h、24 h、48 h 和72 h 后，采用四甲基偶氮唑盐(MTT)法检测 MC 增殖情况，RT - PCR 检测各组MC、GRP78、Caspase -12 mRNA 的表达水平。结果：(1)模型组 MC 在各时间点均明显增殖(P <0．05或 P <0．01)；与模型组比较，中药大、中、小剂量组在24 h、48 h、72 h 均能抑制 MC 增殖(均 P <0．01)，其中以大剂量组效果最佳(P <0．01)；西药组MC 增殖在12 h、24 h 低于中药大剂量组(均 P <0．05)，而在48 h、72 h 两组之间差异无统计学意义(P >0．05)。(2)与正常组比较，模型组 GRP78 mRNA 在24 h、48 h 持续升高，而72 h 明显下降(P <0．05，P <0．01)。四个给药组之间 GRP78 mRNA比较，48 h 时呈西药组>中药小剂量组>中剂量组>大剂量组，72 h 时呈西药组>中药小剂量组>大剂量组(均 P <0．05， P <0．01)。同时各给药组 GRP78 mRNA 表达呈现出从24 h、48 h 到72 h 持续缓慢增加的趋势，表明药物可延缓 GRP78增幅、延缓 ERS 而持续发挥其保护细胞的作用。(3)Caspase -12 mRNA 结果显示：与正常组比较，模型组48 h、72 h 时 Caspase -12 mRNA 明显增加(P <0．01)，而各给药组 Caspase -12 mRNA 均较模型组明显下降(P <0．05或 P <0．01)，48 h 时三个中药组Caspase -12 mRNA 表达明显低于西药组(P <0．05)；72 h 时三个中药组呈小剂量组>中剂量组>大剂量组(P <0．01或 P <0．05)，提示 casspase -12 mRNA 表达与给药剂量呈负相关。结论：高糖条件下大鼠肾小球 MC 内质网应激明显，通络益肾方可明显抑制 MC 的增殖，推测其作用机制与延缓 GRP78增幅、下调 Caspase -12 mRNA 的表达有关。
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